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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
|
|
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|
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|
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|
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|
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, O |
|
and O |
|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
( O |
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|
) O |
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of O |
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the O |
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lanthipeptide O |
|
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( O |
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accession O |
|
number O |
|
AAK67266.1 B-bgc-accession |
|
) O |
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. O |
|
|
|
B O |
|
Comparison O |
|
of O |
|
precursor O |
|
peptides O |
|
of O |
|
plantazolicin O |
|
( O |
|
PlnA O |
|
) O |
|
, O |
|
streptolysin O |
|
S O |
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( O |
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clostridiolysin O |
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S O |
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|
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|
peptides O |
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B. O |
|
intermedia O |
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, O |
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B. O |
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and O |
|
T. O |
|
mathranii O |
|
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|
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site O |
|
of O |
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leader O |
|
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|
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|
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in O |
|
bold O |
|
. O |
|
|
|
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|
A O |
|
potential O |
|
pelgipeptin O |
|
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|
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|
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|
( O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
on O |
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|
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|
pathway O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
substrate O |
|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
and/or O |
|
the O |
|
hydrolase O |
|
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|
before O |
|
being O |
|
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|
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|
( O |
|
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|
hypothesis O |
|
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|
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|
and O |
|
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|
[ O |
|
6 O |
|
] O |
|
) O |
|
. O |
|
|
|
sssA/sssA′/sssA1 O |
|
: O |
|
suicin O |
|
precursor O |
|
; O |
|
sssE O |
|
, O |
|
sssF O |
|
, O |
|
and O |
|
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|
: O |
|
immunity O |
|
proteins O |
|
; O |
|
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|
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|
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|
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|
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|
; O |
|
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|
: O |
|
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|
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|
in O |
|
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|
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|
; O |
|
sssR O |
|
: O |
|
response O |
|
regulator O |
|
; O |
|
sssT O |
|
: O |
|
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|
transporter O |
|
. O |
|
|
|
Also O |
|
, O |
|
several O |
|
loline-alkaloid O |
|
producers O |
|
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|
missing O |
|
or O |
|
inactive O |
|
decoration O |
|
genes O |
|
( O |
|
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|
, O |
|
lolM O |
|
, O |
|
and O |
|
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|
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|
. O |
|
|
|
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|
genes O |
|
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|
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|
as O |
|
a O |
|
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|
gene O |
|
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|
( O |
|
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|
) O |
|
. O |
|
|
|
salmonicida O |
|
A449 O |
|
70 O |
|
YP_001141301 B-bgc-accession |
|
ORF4 O |
|
5237.6016 O |
|
glycosyltransferase O |
|
, O |
|
group O |
|
2 O |
|
family O |
|
protein O |
|
wbxS O |
|
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|
coli O |
|
48 O |
|
ACH97156 B-bgc-accession |
|
ORF5 O |
|
6013.7269 O |
|
integral O |
|
membrane O |
|
protein O |
|
AefA/O-antigen O |
|
flippase O |
|
wzx O |
|
Salmonella O |
|
bongori O |
|
NCTC O |
|
12419 O |
|
70 O |
|
YP_004730750 B-bgc-accession |
|
ORF6 O |
|
7300.9282 O |
|
epimerase/dehydratase O |
|
family O |
|
WbfY-like O |
|
protein O |
|
|
|
wbgZ O |
|
Aeromonas O |
|
hydrophila O |
|
subsp O |
|
. O |
|
|
|
mpz7 O |
|
and O |
|
mpz8 O |
|
show O |
|
similarity O |
|
( O |
|
74 O |
|
% O |
|
and O |
|
60 O |
|
% O |
|
, O |
|
respectively O |
|
) O |
|
to O |
|
monooxygenases O |
|
. O |
|
|
|
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|
lividomycin O |
|
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|
gene O |
|
cluster O |
|
was O |
|
cloned O |
|
from O |
|
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|
lividus O |
|
as O |
|
a O |
|
40 O |
|
kb O |
|
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|
fragment O |
|
( O |
|
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|
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|
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|
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|
. O |
|
|
|
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|
B O |
|
gene O |
|
cluster O |
|
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|
flanked O |
|
at O |
|
both O |
|
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|
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|
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|
genes O |
|
encoding O |
|
ribosomal O |
|
and O |
|
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|
proteins O |
|
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|
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|
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|
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|
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|
2 O |
|
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|
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|
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|
are O |
|
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|
not O |
|
involved O |
|
in O |
|
geninthiocin O |
|
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|
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|
compound O |
|
2 O |
|
biosynthesises O |
|
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|
but O |
|
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|
play O |
|
a O |
|
key O |
|
role O |
|
in O |
|
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|
of O |
|
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|
sp. O |
|
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|
130001 O |
|
. O |
|
|
|
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|
completed O |
|
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|
sequencing O |
|
and O |
|
gene O |
|
function O |
|
annotation O |
|
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|
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|
ustus O |
|
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|
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|
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|
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|
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|
. O |
|
|
|
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|
of O |
|
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|
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|
Overcome O |
|
Drug O |
|
Resistance O |
|
: O |
|
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|
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|
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|
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|
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|
resistance O |
|
, O |
|
especially O |
|
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|
resistance O |
|
, O |
|
is O |
|
a O |
|
growing O |
|
threat O |
|
to O |
|
human O |
|
health O |
|
. O |
|
|
|
griseus]74 O |
|
% O |
|
srcmGIV O |
|
glycosyltransferase391PyrC4 O |
|
[ O |
|
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|
rugosporus]41 O |
|
% O |
|
srcmGII O |
|
glycosyltransferase391SsfS6 O |
|
[ O |
|
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|
sp. O |
|
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|
% O |
|
srcmF O |
|
dTDP-4-keto-6-deoxy-D-glucose O |
|
epimerase199dTDP-4-keto-6-deoxy-D-glucose O |
|
epimerase O |
|
[ O |
|
|
|
Streptomyces O |
|
tsukubensis]78 O |
|
% O |
|
srcmOII O |
|
oxygenase550DacO2 O |
|
|
|
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|
of O |
|
the O |
|
cladoniamide O |
|
and O |
|
BE-54017 O |
|
gene O |
|
clusters O |
|
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|
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|
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|
individual O |
|
genes O |
|
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|
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|
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|
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|
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|
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|
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|
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|
well O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
13 O |
|
] O |
|
. O |
|
|
|
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|
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|
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|
a O |
|
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|
metalloproteinase O |
|
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|
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|
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|
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|
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|
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|
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|
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|
western O |
|
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|
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|
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|
Crotalus O |
|
atrox O |
|
. O |
|
|
|
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|
the O |
|
genes O |
|
MpFasA2 O |
|
, O |
|
MpFasB2 O |
|
, O |
|
MpPKS5 O |
|
, O |
|
mppD O |
|
, O |
|
and O |
|
mppB O |
|
are O |
|
structural O |
|
genes O |
|
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|
pigment O |
|
biosynthesis O |
|
and O |
|
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|
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|
a O |
|
regulatory O |
|
gene O |
|
( O |
|
Balakrishnan O |
|
et O |
|
al. O |
|
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|
) O |
|
, O |
|
the O |
|
polyketide O |
|
chromophores O |
|
and O |
|
media O |
|
fatty O |
|
acid O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
A O |
|
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|
B O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
0.8 O |
|
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|
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|
and O |
|
1.6 O |
|
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|
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|
respectively O |
|
. O |
|
|
|
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|
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|
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|
a O |
|
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|
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|
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|
monobactam O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
a O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
unit O |
|
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|
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|
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|
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|
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|
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|
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|
material O |
|
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|
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|
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|
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|
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|
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|
and O |
|
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|
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|
proteins O |
|
and O |
|
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|
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|
as O |
|
a O |
|
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|
acyl-CoA. O |
|
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|
, O |
|
a O |
|
17.7 O |
|
O O |
|
kb O |
|
swrA O |
|
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|
the O |
|
core O |
|
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|
chain O |
|
( O |
|
the O |
|
structure O |
|
of O |
|
the O |
|
CLP O |
|
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|
a O |
|
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|
acid O |
|
peptide O |
|
moiety O |
|
) O |
|
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|
which O |
|
contains O |
|
a O |
|
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|
of O |
|
five O |
|
modules O |
|
|
|
G-52 O |
|
is O |
|
6-methylsisomicin O |
|
and O |
|
G-418 O |
|
( O |
|
geneticin O |
|
) O |
|
is O |
|
structurally O |
|
similar O |
|
to O |
|
gentamicin O |
|
. O |
|
|
|
Antibiotic O |
|
susceptibility O |
|
of O |
|
S. O |
|
infantarius O |
|
LP90a O |
|
. O |
|
|
|
Gene O |
|
Target O |
|
Primer O |
|
Name O |
|
Primer O |
|
Sequence O |
|
5′ O |
|
to O |
|
3′ O |
|
Amplicon O |
|
Length/bp O |
|
Target O |
|
Species O |
|
Reference O |
|
TRI3 O |
|
3_CONS O |
|
1 O |
|
TGGCAAAGACTGGTTCAC O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
asiaticum O |
|
[ O |
|
79 O |
|
] O |
|
TRI3 O |
|
3_NIV_F O |
|
GTGCACAGAATATACGAGC O |
|
840 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
asiaticum O |
|
[ O |
|
79 O |
|
] O |
|
TRI3 O |
|
3_15ADON_F O |
|
ACTGACCCAAGCTGCCATC O |
|
610 O |
|
F. O |
|
graminearum O |
|
, O |
|
|
|
F. O |
|
asiaticum O |
|
[ O |
|
79 O |
|
] O |
|
TRI3 O |
|
3_3ADON_F O |
|
CGCATTGGCTAACACATG O |
|
243 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
asiaticum O |
|
[ O |
|
79 O |
|
] O |
|
TRI12 O |
|
12_CONS O |
|
CATGAGCATGGTGATGTC O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
asiaticum O |
|
[ O |
|
79 O |
|
] O |
|
TRI12 O |
|
12_NIV_F O |
|
TCTCCTCGTTGTATCTGG O |
|
840 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
asiaticum O |
|
[ O |
|
79 O |
|
] O |
|
TRI12 O |
|
12_15ADON_F O |
|
|
|
TACAGCGGTCGCAACTTC O |
|
670 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
asiaticum O |
|
[ O |
|
79 O |
|
] O |
|
TRI12 O |
|
12_3ADON_F O |
|
CTTTGGCAAGCCCGTGCA O |
|
410 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
asiaticum O |
|
[ O |
|
79 O |
|
] O |
|
TRI3 O |
|
Tri3F971 O |
|
CATCATACTCGCTCTGCTG O |
|
708for O |
|
15-ADON O |
|
producers O |
|
only O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
80 O |
|
] O |
|
Tri3F1325 O |
|
|
|
GCATTGGCTAACACATGA O |
|
354for O |
|
3-ADON O |
|
producers O |
|
only O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
80 O |
|
] O |
|
Tri3R1679 O |
|
TT(A/G)TAGTTTGCA O |
|
TCATT(A/G)TAG O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
80 O |
|
] O |
|
Gene O |
|
F O |
|
3891 O |
|
GCTGTCAYAGYCAGAAGYTACGATG O |
|
1200 O |
|
Fusarium O |
|
incarnatum O |
|
equiseti O |
|
species O |
|
complex O |
|
[ O |
|
62 O |
|
] O |
|
3894 O |
|
|
|
AGAYATGBAGGACARGGCTTAGGGT O |
|
Fusarium O |
|
incarnatum O |
|
equiseti O |
|
species O |
|
complex O |
|
[ O |
|
62 O |
|
] O |
|
TRI1 O |
|
1285 O |
|
GCGTCTCAGCTTCATCAAGGCAKCKAMTGAWTCG O |
|
1200 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
1292 O |
|
CTTGACTTSMTTGGCKGCAAAGAARCGACCA O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
TRI3 O |
|
1912 O |
|
|
|
TGTGTMGGYGCWGAGGCVATYGTTGG O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
1914 O |
|
ACRGCAGCRGTCTGRCACATGGCGTA O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
TRI4 O |
|
2576 O |
|
CCAATCAGYCAYGCTRTTGGGATACTG O |
|
1800 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
2578 O |
|
ACCCGGATTTCRCCAACATGCT O |
|
F. O |
|
|
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
TRI5 O |
|
1558 O |
|
GGCATGGTCGTGTACTCTTGGGTCAAGGT O |
|
1300 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
1559 O |
|
GCCTGMYCAWAGAAYTTGCRGAACTT O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
TRI8 O |
|
3904 O |
|
GACCAGNAYCACSGYCAACAGTTCAG O |
|
1200 O |
|
Fusarium O |
|
incarnatum O |
|
equiseti O |
|
species O |
|
complex O |
|
[ O |
|
62 O |
|
] O |
|
|
|
3906 O |
|
GAACAGCCRCTCCRWAACTATTGTC O |
|
Fusarium O |
|
incarnatum O |
|
equiseti O |
|
species O |
|
complex O |
|
[ O |
|
62 O |
|
] O |
|
TRI11 O |
|
3895 O |
|
TWCCCCACAAGRAACAYCTYGARCT O |
|
1300 O |
|
Fusarium O |
|
incarnatum O |
|
equiseti O |
|
species O |
|
complex O |
|
[ O |
|
62 O |
|
] O |
|
3897 O |
|
TCCCASACTGTYCTSGCMAGCATCAT O |
|
Fusarium O |
|
incarnatum O |
|
equiseti O |
|
species O |
|
complex O |
|
[ O |
|
62 O |
|
] O |
|
TRI16 O |
|
1472b O |
|
CCTCTCTCCCCTTGAYCAATTRAACTCT O |
|
NA O |
|
F. O |
|
graminearum O |
|
, O |
|
|
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
1473b O |
|
CTTCCCGATCCCRAYGAGCCTCTTACAC O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
1474b O |
|
GCCTTATMTKGGTAATGTCGTGCTKACA O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
1475b O |
|
AAGAGGCTCRTYGGGATCGGGAAGGTTC O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
1476b O |
|
|
|
CARCCGACGATGTMAGCACGACATTACC O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
1477b O |
|
CAATATACGGATACCGCACAAAGACTGG O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
TRI101 O |
|
2 O |
|
109 O |
|
CCATGGGTCGCRGGCCARGTSAA O |
|
NA O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
178 O |
|
AACTCSCCRTCIGGYTTYTTNGGCAT O |
|
F. O |
|
graminearum O |
|
, O |
|
|
|
F. O |
|
sporotrichioides O |
|
[ O |
|
30 O |
|
] O |
|
TRI5 O |
|
HATri/F O |
|
CAGATGGAGAACTGGATGGT O |
|
260 O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
poae O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
, O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sambucinum O |
|
[ O |
|
81 O |
|
] O |
|
HATri/R O |
|
GCACAAGTGCCACGTGAC O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
poae O |
|
, O |
|
F. O |
|
sporotrichioides O |
|
, O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
sambucinum O |
|
[ O |
|
81 O |
|
] O |
|
TRI11 O |
|
N11 O |
|
|
|
CTTGTCAGGCGGCACAGTAG O |
|
643 O |
|
for O |
|
NIV-producers O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
mesoamericanum O |
|
, O |
|
F. O |
|
cortaderiae O |
|
, O |
|
F. O |
|
gerlachii O |
|
, O |
|
F. O |
|
meridionale O |
|
× O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
meridionale O |
|
, O |
|
F. O |
|
lunulosporum O |
|
, O |
|
F. O |
|
cerealis O |
|
, O |
|
F. O |
|
vorosii O |
|
, O |
|
F. O |
|
aethiopicum O |
|
, O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
boothii O |
|
, O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
brasilicum O |
|
, O |
|
F. O |
|
|
|
austroamericanum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
pseudograminearum O |
|
[ O |
|
74 O |
|
] O |
|
15D11 O |
|
AAGTATGGTCCAGTTGTCCGTATT O |
|
424 O |
|
for O |
|
3-ADON O |
|
producers O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
mesoamericanum O |
|
, O |
|
F. O |
|
cortaderiae O |
|
, O |
|
F. O |
|
gerlachii O |
|
, O |
|
F. O |
|
meridionale O |
|
× O |
|
F. O |
|
asiaticu O |
|
) O |
|
, O |
|
F. O |
|
meridionale O |
|
, O |
|
F. O |
|
lunulosporum O |
|
, O |
|
F. O |
|
cerealis O |
|
, O |
|
F. O |
|
vorosii O |
|
, O |
|
F. O |
|
aethiopicum O |
|
, O |
|
|
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
boothii O |
|
, O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
brasilicum O |
|
, O |
|
F. O |
|
austroamericanum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
pseudograminearum O |
|
[ O |
|
74 O |
|
] O |
|
3D11 O |
|
GCAA O |
|
GTCTGGCGAGGCC O |
|
342 O |
|
for O |
|
15-ADON O |
|
producers O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
mesoamericanum O |
|
, O |
|
F. O |
|
cortaderiae O |
|
, O |
|
F. O |
|
gerlachii O |
|
, O |
|
F. O |
|
meridionale O |
|
× O |
|
F. O |
|
asiaticu O |
|
) O |
|
, O |
|
F. O |
|
meridionale O |
|
, O |
|
F. O |
|
|
|
lunulosporum O |
|
, O |
|
F. O |
|
cerealis O |
|
, O |
|
F. O |
|
vorosii O |
|
, O |
|
F. O |
|
aethiopicum O |
|
, O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
boothii O |
|
, O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
brasilicum O |
|
, O |
|
F. O |
|
austroamericanum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
pseudograminearum O |
|
[ O |
|
74 O |
|
] O |
|
11R O |
|
TCAAAGGCCAGAGCA O |
|
ACCC O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
mesoamericanum O |
|
, O |
|
F. O |
|
cortaderiae O |
|
, O |
|
F. O |
|
gerlachii O |
|
, O |
|
F. O |
|
meridionale O |
|
× O |
|
|
|
F. O |
|
asiaticu O |
|
) O |
|
, O |
|
F. O |
|
meridionale O |
|
, O |
|
F. O |
|
lunulosporum O |
|
, O |
|
F. O |
|
cerealis O |
|
, O |
|
F. O |
|
vorosii O |
|
, O |
|
F. O |
|
aethiopicum O |
|
, O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
boothii O |
|
, O |
|
F. O |
|
asiaticum O |
|
, O |
|
F. O |
|
brasilicum O |
|
, O |
|
F. O |
|
austroamericanum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
pseudograminearum O |
|
[ O |
|
74 O |
|
] O |
|
TRI11 O |
|
Tri11-CON O |
|
GACTGCTCATGGAGACGCTG O |
|
NA O |
|
F. O |
|
graminearum O |
|
[ O |
|
82 O |
|
] O |
|
Tri11 O |
|
- O |
|
|
|
3AcDON O |
|
TCCTCATGCTCG O |
|
GTGGACTCG O |
|
334 O |
|
F. O |
|
graminearum O |
|
[ O |
|
82 O |
|
] O |
|
Tri11 O |
|
- O |
|
15AcDON O |
|
TGGTCCAGT O |
|
TGTCCGTATT O |
|
279 O |
|
F. O |
|
graminearum O |
|
[ O |
|
82 O |
|
] O |
|
Tri11-NIV O |
|
GTAGGTTCCATTGC O |
|
TTGTTC O |
|
497 O |
|
F. O |
|
graminearum O |
|
[ O |
|
82 O |
|
] O |
|
TRI7 O |
|
GzTri7/f1 O |
|
GGCTTTACGACTCCTCAACAATGG O |
|
∼160 O |
|
F. O |
|
graminearum O |
|
[ O |
|
66 O |
|
] O |
|
GzTri7/r1 O |
|
|
|
AGAGCCCTGCGAAAG(C/T)ACTGGTGC O |
|
F. O |
|
graminearum O |
|
[ O |
|
66 O |
|
] O |
|
TRI7 O |
|
Tri7F340 O |
|
ATCGTGTACAAGGTTTACG O |
|
625 O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
80 O |
|
] O |
|
Tri7R965 O |
|
TTCAAGTAACGTTCGACAAT O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
80 O |
|
] O |
|
TRI13 O |
|
Tri13F O |
|
|
|
CATCATGAGACTTGTKCRGTTTGGG O |
|
1075 O |
|
for O |
|
NIV O |
|
producers;799 O |
|
for O |
|
DON-producers O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
83 O |
|
] O |
|
Tri13DONR O |
|
GCTAGATCGATTGTTGCATTGAG O |
|
282 O |
|
for O |
|
DON O |
|
producers O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
83 O |
|
] O |
|
Tri13R O |
|
TTGAAAGCTCCAATGTCGTG O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
83 O |
|
|
|
] O |
|
Tri13NIVF O |
|
CCAAATCCGAAAACCGCAG O |
|
312 O |
|
for O |
|
NIV O |
|
producers O |
|
F. O |
|
graminearum O |
|
, O |
|
F. O |
|
culmorum O |
|
, O |
|
F. O |
|
cerealis O |
|
[ O |
|
83 O |
|
] O |
|
|
|
The O |
|
deduced O |
|
protein O |
|
sequence O |
|
( O |
|
Table O |
|
2 O |
|
) O |
|
from O |
|
cesH O |
|
( O |
|
31 O |
|
kDa O |
|
) O |
|
showed O |
|
significant O |
|
( O |
|
58 O |
|
% O |
|
) O |
|
identity O |
|
to O |
|
putative O |
|
hydrolases/acyltransferases O |
|
( O |
|
COG0596 O |
|
) O |
|
from O |
|
B. O |
|
cereus O |
|
group O |
|
members O |
|
. O |
|
|
|
carotovorum O |
|
PC1 O |
|
52 O |
|
YP_003016893 B-bgc-accession |
|
ORF16 O |
|
17986.19167 O |
|
glycosyl O |
|
transferase O |
|
group O |
|
1 O |
|
wbxI O |
|
Methylobacter O |
|
tundripaludum O |
|
SV96 O |
|
52 O |
|
ZP_08780763 B-bgc-accession |
|
ORF17 O |
|
19164.19655 O |
|
acetyltransferase O |
|
wcaF O |
|
Methylobacter O |
|
tundripaludum O |
|
SV96 O |
|
59 O |
|
ZP_08780764 B-bgc-accession |
|
ORF18 O |
|
19648.20826 O |
|
O-antigen O |
|
polymerase O |
|
wzyE O |
|
Bacteroides O |
|
|
|
sp. O |
|
2_1_7 O |
|
29 O |
|
ZP_05287114 B-bgc-accession |
|
ORF19 O |
|
20877.21968 O |
|
group O |
|
1 O |
|
glycosyl O |
|
transferase O |
|
protein O |
|
wdaN O |
|
Dysgonomonas O |
|
gadei O |
|
ATCC O |
|
BAA-286 O |
|
42 O |
|
ZP_08475479 B-bgc-accession |
|
ORF20 O |
|
22444.23694 O |
|
O-antigen O |
|
flippase O |
|
wzxB O |
|
Shewanella O |
|
baltica O |
|
OS625 O |
|
81 O |
|
EHC06312 B-bgc-accession |
|
ORF21 O |
|
23691.24794 O |
|
aminotransferase O |
|
fdtB O |
|
Shewanella O |
|
baltica O |
|
OS195 O |
|
|
|
81 O |
|
YP_001555451 B-bgc-accession |
|
ORF22 O |
|
24796.25233 O |
|
dTDP-D-Fucp3N O |
|
acetyltransferase O |
|
fdtC O |
|
Shewanella O |
|
baltica O |
|
OS195 O |
|
85 O |
|
YP_001555452 B-bgc-accession |
|
ORF23 O |
|
25235.25657 O |
|
dTDP-6-deoxy-3,4-keto-hexulose O |
|
isomerase O |
|
fdtA O |
|
Shewanella O |
|
putrefaciens O |
|
200 O |
|
72 O |
|
ADV52549 B-bgc-accession |
|
ORF24 O |
|
25668.26534 O |
|
glucose-1-phosphate O |
|
|
|
thymidylyltransferase O |
|
rmlA O |
|
Shewanella O |
|
putrefaciens O |
|
200 O |
|
79 O |
|
ADV52548 B-bgc-accession |
|
ORF25 O |
|
26531.27619 O |
|
dTDP-glucose-4 O |
|
- O |
|
6-dehydratase O |
|
rmlB O |
|
Aeromonas O |
|
hydrophila O |
|
93 O |
|
AAM22544 B-bgc-accession |
|
ORFd O |
|
28234.31383 O |
|
AcrB O |
|
protein O |
|
acrB O |
|
Aeromonas O |
|
hydrophila O |
|
subsp O |
|
. O |
|
|
|
The O |
|
chromatograms O |
|
of O |
|
Au8003 O |
|
reaction O |
|
product O |
|
ophiobolin O |
|
F O |
|
extracted O |
|
at O |
|
m/z O |
|
358 O |
|
( O |
|
a O |
|
) O |
|
: O |
|
( O |
|
I O |
|
) O |
|
GGPP+IPP O |
|
, O |
|
( O |
|
II O |
|
) O |
|
FPP+IPP O |
|
, O |
|
( O |
|
III O |
|
) O |
|
GPP+IPP O |
|
, O |
|
( O |
|
IV O |
|
) O |
|
DMAPP+IPP O |
|
and O |
|
( O |
|
V O |
|
) O |
|
IPP O |
|
, O |
|
and O |
|
MS O |
|
Spectra O |
|
of O |
|
peak O |
|
1 O |
|
( O |
|
b O |
|
) O |
|
; O |
|
chromatograms O |
|
of O |
|
Au13192 O |
|
reaction O |
|
product O |
|
veridiene O |
|
extracted O |
|
at O |
|
m/z O |
|
272 O |
|
( O |
|
c O |
|
) O |
|
: O |
|
( O |
|
I O |
|
) O |
|
FPP+IPP O |
|
, O |
|
( O |
|
II O |
|
) O |
|
|
|
GPP+IPP O |
|
, O |
|
( O |
|
III O |
|
) O |
|
DMAPP+IPP O |
|
, O |
|
( O |
|
IV O |
|
) O |
|
IPP O |
|
and O |
|
MS O |
|
Spectra O |
|
of O |
|
peak O |
|
2 O |
|
( O |
|
d O |
|
) O |
|
; O |
|
chromatograms O |
|
of O |
|
phosphatase O |
|
hydolysate O |
|
of O |
|
Au6298 O |
|
reaction O |
|
product O |
|
FPP O |
|
extracted O |
|
at O |
|
m/z O |
|
222 O |
|
( O |
|
e O |
|
) O |
|
: O |
|
( O |
|
I O |
|
) O |
|
DMAPP+IPP O |
|
, O |
|
( O |
|
II O |
|
) O |
|
IPP O |
|
only O |
|
and O |
|
MS O |
|
Spectra O |
|
of O |
|
peak O |
|
3 O |
|
( O |
|
f O |
|
) O |
|
. O |
|
|
|
For O |
|
myeD O |
|
, O |
|
which O |
|
encodes O |
|
an O |
|
amidohydrolase O |
|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
|
|
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|
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|
|
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|
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|
|
|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
jinggangensis O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
ARTR00000000 B-bgc-accession |
|
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|
, O |
|
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|
sp. O |
|
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|
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|
AGNH00000000 B-bgc-accession |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
CADY00000000 O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
, O |
|
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|
albus O |
|
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|
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|
NC_020990 O |
|
|
|
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|
sp. O |
|
SM8 O |
|
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|
AMPN00000000 B-bgc-accession |
|
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|
, O |
|
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|
sp. O |
|
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|
( O |
|
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|
) O |
|
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|
( O |
|
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|
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|
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|
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|
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|
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|
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|
) O |
|
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|
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|
sp. O |
|
LaPpAH-202 O |
|
( B-bgc-accession |
|
ARDM00000000 O |
|
) O |
|
, O |
|
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|
sp. O |
|
CNY228 O |
|
( B-bgc-accession |
|
ARIN01000033 O |
|
) O |
|
|
|
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|
phoRP O |
|
system O |
|
of O |
|
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|
filipinensis O |
|
was O |
|
cloned O |
|
and O |
|
transcriptionally O |
|
characterised O |
|
. O |
|
|
|
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|
linear O |
|
cylindrocyclophane-related O |
|
cylindrofridins O |
|
28‒30 O |
|
also O |
|
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|
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|
activity O |
|
in O |
|
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|
low O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
presence O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
three O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
potential O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
synthesized O |
|
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|
different O |
|
combinations O |
|
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|
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|
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|
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|
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|
and O |
|
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|
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|
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|
activity O |
|
[ O |
|
63,64 O |
|
] O |
|
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|
ultimately O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
by O |
|
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|
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|
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|
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|
the O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
the O |
|
14 O |
|
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|
hydrophila O |
|
O O |
|
antigen O |
|
gene O |
|
clusters O |
|
have O |
|
been O |
|
deposited O |
|
in O |
|
the O |
|
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|
database O |
|
with O |
|
accession O |
|
numbers O |
|
MH449673 B-bgc-accession |
|
to I-bgc-accession |
|
MH449686 I-bgc-accession |
|
. O |
|
|
|
MMAR_2474 O |
|
protein O |
|
exceptionally O |
|
biosynthesized O |
|
methylated O |
|
alkyl-resorcinol O |
|
and O |
|
methylated O |
|
acyl-phloroglucinol O |
|
products O |
|
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|
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|
same O |
|
catalytic O |
|
core O |
|
. O |
|
|
|
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|
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|
gene O |
|
cluster O |
|
was O |
|
cloned O |
|
as O |
|
a O |
|
90 O |
|
kb O |
|
DNA O |
|
fragment O |
|
[ O |
|
377,378 O |
|
] O |
|
( O |
|
GB O |
|
No. O |
|
AJ862840 B-bgc-accession |
|
) O |
|
. O |
|
|
|
Furthermore O |
|
, O |
|
in O |
|
flowers O |
|
the O |
|
sesquiterpenes O |
|
compounds O |
|
were O |
|
observed O |
|
to O |
|
be O |
|
the O |
|
main O |
|
group O |
|
( O |
|
0.42 O |
|
% O |
|
) O |
|
, O |
|
followed O |
|
by O |
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one O |
|
diterpene O |
|
compound O |
|
( O |
|
0.01 O |
|
% O |
|
) O |
|
. O |
|
|
|
GenBank O |
|
accession O |
|
numbers O |
|
: O |
|
M87280 B-bgc-accession |
|
for O |
|
Pantoa O |
|
agglomerans O |
|
, O |
|
CP001875 B-bgc-accession |
|
for O |
|
Pantoa O |
|
ananatis O |
|
, O |
|
and O |
|
LC317091 B-bgc-accession |
|
and O |
|
LC317092 B-bgc-accession |
|
for O |
|
Pseudomonas O |
|
sp. O |
|
strain O |
|
Akiakane O |
|
[ O |
|
48 O |
|
] O |
|
A O |
|
common O |
|
strategy O |
|
to O |
|
improve O |
|
the O |
|
yield O |
|
is O |
|
the O |
|
optimization O |
|
of O |
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culture O |
|
conditions O |
|
[ O |
|
73 O |
|
] O |
|
. O |
|
|
|
Ergot O |
|
alkaloid O |
|
( O |
|
EAS O |
|
) O |
|
loci O |
|
In O |
|
the O |
|
scaffolded O |
|
assemblies O |
|
of O |
|
the O |
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|
purpurea O |
|
and O |
|
E. O |
|
festucae O |
|
Fl1 O |
|
genomes O |
|
, O |
|
and O |
|
the O |
|
scaffolded O |
|
E2368 O |
|
assembly O |
|
of O |
|
2010 O |
|
- O |
|
06 O |
|
, O |
|
the O |
|
EAS O |
|
genes O |
|
were O |
|
clustered O |
|
within O |
|
individual O |
|
supercontigs O |
|
( O |
|
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|
6 O |
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) O |
|
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|
|
|
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|
three O |
|
genes O |
|
are O |
|
clustered O |
|
with O |
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two O |
|
other O |
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ORFs O |
|
that O |
|
encode O |
|
a O |
|
putative O |
|
extracellular O |
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serine O |
|
protease O |
|
( O |
|
subP O |
|
) O |
|
and O |
|
an O |
|
ABC O |
|
transporter O |
|
( O |
|
subT O |
|
) O |
|
, O |
|
respectively O |
|
. O |
|
|
|
Streptomyces O |
|
viridochromogenes O |
|
DSM O |
|
40736 O |
|
S. O |
|
viridochromogenes O |
|
is O |
|
a O |
|
producer O |
|
of O |
|
avilamycin O |
|
A O |
|
, O |
|
an O |
|
oligosaccharide O |
|
antibiotic O |
|
. O |
|
|
|
Although O |
|
clinical O |
|
detection O |
|
, O |
|
epidemiological O |
|
surveillance O |
|
, O |
|
and O |
|
tracing O |
|
of O |
|
pathogenic O |
|
bacteria O |
|
are O |
|
typically O |
|
done O |
|
using O |
|
serotyping O |
|
methods O |
|
that O |
|
rely O |
|
on O |
|
identifying O |
|
bacterial O |
|
surface O |
|
O O |
|
antigens O |
|
through O |
|
agglutination O |
|
reactions O |
|
with O |
|
antisera O |
|
, O |
|
molecular O |
|
methods O |
|
such O |
|
as O |
|
the O |
|
one O |
|
we O |
|
have O |
|
developed O |
|
may O |
|
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|
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|
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|
more O |
|
cost O |
|
effective O |
|
. O |
|
|
|
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|
amplified O |
|
the O |
|
Au13192 O |
|
coding O |
|
gene O |
|
, O |
|
which O |
|
contained O |
|
nine O |
|
exons O |
|
, O |
|
by O |
|
overlap O |
|
extension O |
|
PCR O |
|
( O |
|
Supplementary O |
|
Fig. O |
|
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|
, O |
|
Table O |
|
S8 O |
|
) O |
|
using O |
|
A. O |
|
ustus O |
|
094102 O |
|
genomic O |
|
DNA O |
|
as O |
|
template O |
|
. O |
|
|
|
Functional O |
|
characterization O |
|
of O |
|
terpene O |
|
synthase O |
|
genes O |
|
in O |
|
transgenic O |
|
A. O |
|
thaliana O |
|
leaves O |
|
To O |
|
test O |
|
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|
thaliana O |
|
in O |
|
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|
transgenic O |
|
expression O |
|
system O |
|
for O |
|
the O |
|
production O |
|
of O |
|
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|
terpenes O |
|
, O |
|
the O |
|
following O |
|
genes O |
|
were O |
|
selected O |
|
from O |
|
S. O |
|
guaranitica O |
|
: O |
|
farnesyl O |
|
pyrophosphate O |
|
synthases O |
|
( O |
|
FPPS O |
|
) O |
|
, O |
|
geranyl O |
|
diphosphate O |
|
synthases O |
|
( O |
|
GPPS O |
|
) O |
|
and O |
|
(3S)-linalool O |
|
synthase O |
|
( O |
|
LINS O |
|
) O |
|
encoded O |
|
by O |
|
SgFPPS O |
|
, O |
|
SgGPPS O |
|
and O |
|
SgLINS O |
|
, O |
|
respectively O |
|
. O |
|
|
|
Gene O |
|
arrangement O |
|
, O |
|
functional O |
|
annotation O |
|
and O |
|
domain O |
|
structure O |
|
of O |
|
the O |
|
puw O |
|
gene O |
|
cluster O |
|
( O |
|
56.7 O |
|
kbp O |
|
) O |
|
from O |
|
Cylindrospermum O |
|
alatosporum O |
|
CCALA O |
|
988 O |
|
. O |
|
|
|
NMR O |
|
spectroscopic O |
|
investigations O |
|
in O |
|
comparison O |
|
to O |
|
the O |
|
educt O |
|
1-hydroxyphenazine O |
|
confirmed O |
|
that O |
|
product O |
|
3 O |
|
was O |
|
1-hydroxy-4-dimethylallyl-phenazine O |
|
( O |
|
Figure O |
|
5 O |
|
) O |
|
. O |
|
|
|
However O |
|
, O |
|
the O |
|
toxins O |
|
that O |
|
have O |
|
been O |
|
discussed O |
|
here O |
|
are O |
|
mainly O |
|
peptides O |
|
or O |
|
proteins O |
|
in O |
|
nature O |
|
, O |
|
except O |
|
for O |
|
tetrodotoxin O |
|
, O |
|
saxitoxin O |
|
, O |
|
lipophilic O |
|
alkaloids O |
|
, O |
|
and O |
|
batrachotoxin O |
|
. O |
|
|
|
The O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
was O |
|
cloned O |
|
[ O |
|
72 O |
|
] O |
|
( O |
|
GB O |
|
No. O |
|
AM409314 B-bgc-accession |
|
) O |
|
. O |
|
|
|
Interestingly O |
|
, O |
|
the O |
|
lps O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
of O |
|
Xcc O |
|
, O |
|
which O |
|
comprises O |
|
fifteen O |
|
genes O |
|
, O |
|
is O |
|
also O |
|
located O |
|
between O |
|
the O |
|
metB O |
|
and O |
|
etfA O |
|
genes O |
|
[ O |
|
24 O |
|
] O |
|
. O |
|
|
|
Anthracimycin O |
|
( O |
|
1 O |
|
) O |
|
was O |
|
obtained O |
|
from O |
|
the O |
|
4 O |
|
liter O |
|
fermentation O |
|
of O |
|
N. O |
|
kunsanensis O |
|
with O |
|
impurities O |
|
, O |
|
but O |
|
was O |
|
found O |
|
to O |
|
have O |
|
a O |
|
comparable O |
|
1H O |
|
NMR O |
|
spectra O |
|
( O |
|
Table O |
|
1 O |
|
, O |
|
Supplementary O |
|
Figure O |
|
S1a O |
|
and O |
|
b O |
|
) O |
|
as O |
|
our O |
|
anthracimycin O |
|
standard O |
|
that O |
|
we O |
|
purified O |
|
from O |
|
Streptomyces O |
|
sp. O |
|
T676 O |
|
. O |
|
|
|
In O |
|
Europe O |
|
Aphanizomenon O |
|
gracile O |
|
and O |
|
Cuspidothrix O |
|
issatschenkoi O |
|
are O |
|
the O |
|
only O |
|
known O |
|
producers O |
|
of O |
|
PSP O |
|
toxins O |
|
and O |
|
are O |
|
found O |
|
in O |
|
Southwest O |
|
and O |
|
Central O |
|
European O |
|
freshwater O |
|
bodies O |
|
. O |
|
|
|
Two O |
|
resistance-related O |
|
genes O |
|
, O |
|
otrA O |
|
and O |
|
otrB O |
|
, O |
|
are O |
|
present O |
|
at O |
|
both O |
|
ends O |
|
. O |
|
|
|
Thus O |
|
, O |
|
at O |
|
least O |
|
two O |
|
proteins O |
|
, O |
|
MccC O |
|
and O |
|
MccE O |
|
, O |
|
are O |
|
implicated O |
|
in O |
|
the O |
|
self-resistance O |
|
of O |
|
the O |
|
producing O |
|
strains O |
|
to O |
|
microcin O |
|
C. O |
|
Furthermore O |
|
, O |
|
MccF O |
|
also O |
|
involves O |
|
in O |
|
self-immunity O |
|
[ O |
|
133,134 O |
|
] O |
|
. O |
|
|
|
Whole O |
|
genome O |
|
shotgun O |
|
sequencing O |
|
was O |
|
also O |
|
conducted O |
|
on O |
|
the O |
|
genomes O |
|
of O |
|
the O |
|
clover O |
|
black O |
|
patch O |
|
pathogen O |
|
, O |
|
Slafractonia O |
|
leguminicola O |
|
( O |
|
Alhawatema O |
|
et O |
|
al. O |
|
2015 O |
|
) O |
|
, O |
|
and O |
|
the O |
|
endophyte O |
|
, O |
|
Alternaria O |
|
oxytropis O |
|
( O |
|
Pryor O |
|
et O |
|
al. O |
|
2009 O |
|
) O |
|
, O |
|
both O |
|
of O |
|
which O |
|
are O |
|
known O |
|
swainsonine O |
|
producers O |
|
in O |
|
the O |
|
order O |
|
Pleosporales O |
|
. O |
|
|
|
aurantiaca O |
|
DSM O |
|
19603 O |
|
T O |
|
196 O |
|
368 O |
|
, O |
|
257 O |
|
, O |
|
219 O |
|
2-hydroxy-phenazine O |
|
[42]c O |
|
224 O |
|
371 O |
|
, O |
|
249 O |
|
, O |
|
215 O |
|
phenazine-1-carboxylic O |
|
acid O |
|
[41]c O |
|
DSM O |
|
50083 O |
|
T O |
|
Pseudomonas O |
|
chlororaphis O |
|
subsp O |
|
. O |
|
|
|
The O |
|
exact O |
|
function O |
|
of O |
|
these O |
|
proteins O |
|
, O |
|
MmpL4a O |
|
and O |
|
MmpL4b O |
|
, O |
|
is O |
|
not O |
|
known O |
|
in O |
|
detail O |
|
although O |
|
a O |
|
recent O |
|
study O |
|
performed O |
|
in O |
|
M. O |
|
tuberculosis O |
|
suggests O |
|
that O |
|
MmpL O |
|
proteins O |
|
( O |
|
MmpL7 O |
|
) O |
|
may O |
|
channel O |
|
the O |
|
polyketide O |
|
products O |
|
during O |
|
their O |
|
synthesis O |
|
by O |
|
the O |
|
polyketide O |
|
synthase O |
|
, O |
|
coupling O |
|
synthesis O |
|
and O |
|
export O |
|
[ O |
|
28 O |
|
] O |
|
. O |
|
|
|
The O |
|
samples O |
|
were O |
|
subjected O |
|
to O |
|
alcohol O |
|
series O |
|
dehydration O |
|
( O |
|
50–100 O |
|
% O |
|
ethanol O |
|
) O |
|
and O |
|
then O |
|
chemically O |
|
dried O |
|
using O |
|
hexamethyldisilazane O |
|
Amplification O |
|
and O |
|
analysis O |
|
of O |
|
a O |
|
zeaxanthin O |
|
diglucoside O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
from O |
|
Pseudomonas O |
|
sp. O |
|
102515 O |
|
As O |
|
described O |
|
above O |
|
, O |
|
P. O |
|
psychrotolerans O |
|
is O |
|
the O |
|
closest O |
|
relative O |
|
strain O |
|
to O |
|
Pseudomonas O |
|
sp. O |
|
102515 O |
|
. O |
|
|
|
Notably O |
|
, O |
|
inactivation O |
|
of O |
|
rdmA O |
|
and O |
|
overexpression O |
|
of O |
|
rdmF O |
|
led O |
|
to O |
|
increased O |
|
production O |
|
of O |
|
RDM O |
|
A O |
|
by O |
|
~ O |
|
O O |
|
2.0-fold O |
|
and O |
|
~ O |
|
O O |
|
2.5-fold O |
|
, O |
|
reaching O |
|
yields O |
|
of O |
|
155.3 O |
|
O O |
|
± O |
|
O O |
|
1.89 O |
|
and O |
|
184.8 O |
|
O O |
|
± O |
|
|
|
Table O |
|
5 O |
|
Detected O |
|
LAP O |
|
gene O |
|
cluster O |
|
PhylumLocus O |
|
Tag O |
|
of O |
|
dehydrogenaseSimilar O |
|
to O |
|
† O |
|
Reference O |
|
# O |
|
Clostridium O |
|
botulinum O |
|
A2 O |
|
BoNT/A2 O |
|
Kyoto-FFirmicutes O |
|
CLM_0573 O |
|
clostridiolysin O |
|
S O |
|
Clostridium O |
|
botulinum O |
|
A O |
|
BoNT/A1 O |
|
ATCC O |
|
19397Firmicutes O |
|
CLB_0528 O |
|
clostridiolysin O |
|
S O |
|
Clostridium O |
|
botulinum O |
|
A O |
|
BoNT/A1 O |
|
HallFirmicutes O |
|
CLC_0561 O |
|
|
|
clostridiolysin O |
|
S O |
|
Clostridium O |
|
botulinum O |
|
BoNT/B1 O |
|
OkraFirmicutes O |
|
CLD_0261 O |
|
clostridiolysin O |
|
S O |
|
Clostridium O |
|
botulinum O |
|
BoNT/A3 O |
|
Loch O |
|
MareeFirmicutes O |
|
CLK_3698 O |
|
clostridiolysin O |
|
S O |
|
Clostridium O |
|
botulinum O |
|
Ba4 O |
|
str O |
|
. O |
|
|
|
Kirromycin O |
|
shows O |
|
strong O |
|
antibacterial O |
|
activity O |
|
against O |
|
Streptococci O |
|
, O |
|
some O |
|
Enterococci O |
|
, O |
|
Neisseria O |
|
, O |
|
and O |
|
Haemophilus O |
|
, O |
|
but O |
|
not O |
|
to O |
|
S. O |
|
aureus O |
|
. O |
|
|
|
Staphylococcus O |
|
epidermidis O |
|
plasmid O |
|
SAP106A O |
|
YP_006939047.1 B-bgc-accession |
|
SAP106A_001 O |
|
41 O |
|
Unknown O |
|
LanM O |
|
14 O |
|
. O |
|
|
|
Lechevalieria O |
|
aerocolonigenes O |
|
myeP O |
|
( O |
|
75/83 O |
|
) O |
|
Tryptophan O |
|
halogenase O |
|
mymQ O |
|
411 O |
|
KynU O |
|
, O |
|
NP_250770.1 B-bgc-accession |
|
( O |
|
44/60 O |
|
) O |
|
; O |
|
Pseudomonas O |
|
aeruginosa O |
|
PAO1 O |
|
myeQ O |
|
( O |
|
51/64 O |
|
) O |
|
Kynureninase O |
|
( O |
|
KYN O |
|
) O |
|
mymR3 O |
|
691 O |
|
SBU95407.1 B-bgc-accession |
|
( O |
|
56/67 O |
|
) O |
|
; O |
|
Streptomyces O |
|
sp. O |
|
OspMP-M45 O |
|
myeR3 O |
|
( O |
|
57/68 O |
|
) O |
|
SARP O |
|
family O |
|
transcriptional O |
|
regulator O |
|
|
|
orf-3 O |
|
38 O |
|
None O |
|
predicted O |
|
in O |
|
NCBI O |
|
- O |
|
Unknown O |
|
|
|
Results O |
|
and O |
|
Discussion O |
|
Xanthomonad-inhibitory O |
|
Activity O |
|
of O |
|
P. O |
|
putida O |
|
BW11M1 O |
|
Screening O |
|
of O |
|
a O |
|
collection O |
|
of O |
|
Pseudomonas O |
|
strains O |
|
isolated O |
|
from O |
|
tropical O |
|
crop O |
|
roots O |
|
[ O |
|
33 O |
|
] O |
|
revealed O |
|
a O |
|
broad O |
|
xanthomonad-inhibitory O |
|
activity O |
|
for O |
|
the O |
|
banana O |
|
rhizosphere O |
|
isolate O |
|
P. O |
|
putida O |
|
BW11M1 O |
|
. O |
|
|
|
At O |
|
the O |
|
downstream O |
|
of O |
|
PKS O |
|
genes O |
|
, O |
|
the O |
|
genes O |
|
involved O |
|
in O |
|
the O |
|
biosynthesis O |
|
of O |
|
methoxymalonyl-CoA O |
|
from O |
|
glycerol O |
|
as O |
|
a O |
|
polyketide O |
|
precursor O |
|
( O |
|
Chan O |
|
and O |
|
Thomas O |
|
2010 O |
|
) O |
|
were O |
|
also O |
|
found O |
|
from O |
|
BafAI O |
|
to O |
|
BafAV O |
|
. O |
|
|
|
Similar O |
|
to O |
|
other O |
|
lasso O |
|
peptides O |
|
, O |
|
LarA O |
|
is O |
|
the O |
|
precursor O |
|
peptide O |
|
which O |
|
is O |
|
processed O |
|
by O |
|
LarB O |
|
, O |
|
LarC O |
|
and O |
|
LarD O |
|
and O |
|
then O |
|
exported O |
|
by O |
|
the O |
|
transporter O |
|
LarF O |
|
[ O |
|
73 O |
|
] O |
|
. O |
|
|
|
Similarly O |
|
BAGEL4 O |
|
uses O |
|
HMM O |
|
to O |
|
detect O |
|
core O |
|
RiPP O |
|
encoding O |
|
genes O |
|
, O |
|
however O |
|
, O |
|
it O |
|
is O |
|
independent O |
|
from O |
|
the O |
|
genome O |
|
ORF O |
|
calls O |
|
, O |
|
enabling O |
|
it O |
|
to O |
|
better O |
|
detect O |
|
the O |
|
small O |
|
precursor O |
|
peptides O |
|
found O |
|
in O |
|
RiPP O |
|
encoding O |
|
gene O |
|
clusters O |
|
. O |
|
|
|
Brominated O |
|
derivatives O |
|
1 O |
|
C38H57BrN2O8 O |
|
747.3216 O |
|
d O |
|
747.3226 O |
|
1.3 O |
|
88.0 O |
|
11 O |
|
OCONH2 O |
|
CH3 O |
|
OCONH2 O |
|
CH2Br O |
|
Carbamidocyclophane O |
|
M O |
|
( O |
|
1 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
t.s O |
|
. O |
|
] O |
|
2 O |
|
C38H56Br2N2O8 O |
|
825.2336 O |
|
d O |
|
825.2331 O |
|
0.6 O |
|
100 O |
|
11 O |
|
OCONH2 O |
|
CH2Br O |
|
OCONH2 O |
|
CH2Br O |
|
Carbamidocyclophane O |
|
N O |
|
( O |
|
2 O |
|
) O |
|
e O |
|
, O |
|
|
|
[ O |
|
t.s O |
|
. O |
|
] O |
|
3 O |
|
C38H56Br2N2O8 O |
|
825.2340 O |
|
d O |
|
825.2331 O |
|
1.1 O |
|
100 O |
|
11 O |
|
OCONH2 O |
|
CH3 O |
|
OCONH2 O |
|
CHBr2 O |
|
Carbamidocyclophane O |
|
O O |
|
( O |
|
3 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
t.s O |
|
. O |
|
] O |
|
4 O |
|
C38H55Br3N2O8 O |
|
903.1425 O |
|
d O |
|
903.1436 O |
|
1.2 O |
|
100 O |
|
11 O |
|
OCONH2 O |
|
CH2Br O |
|
OCONH2 O |
|
CHBr2 O |
|
Carbamidocyclophane O |
|
P O |
|
( O |
|
4 O |
|
) O |
|
e O |
|
|
|
, O |
|
[ O |
|
t.s O |
|
. O |
|
] O |
|
5 O |
|
C38H54Br4N2O8 O |
|
981.0529 O |
|
d O |
|
981.0541 O |
|
1.2 O |
|
99.1 O |
|
11 O |
|
OCONH2 O |
|
CHBr2 O |
|
OCONH2 O |
|
CHBr2 O |
|
Carbamidocyclophane O |
|
Q O |
|
( O |
|
5 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
t.s O |
|
. O |
|
] O |
|
6 O |
|
C37H56BrNO7 O |
|
704.3173 O |
|
d O |
|
704.3167 O |
|
0.9 O |
|
100 O |
|
10 O |
|
OCONH2 O |
|
CH3 O |
|
OH O |
|
CH2Br O |
|
Carbamidocyclophane O |
|
R O |
|
( O |
|
6 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
|
|
t.s O |
|
. O |
|
] O |
|
7 O |
|
C37H55Br2NO7 O |
|
782.2266 O |
|
d O |
|
782.2272 O |
|
0.8 O |
|
95.0 O |
|
10 O |
|
OCONH2 O |
|
CH3 O |
|
OH O |
|
CHBr2 O |
|
Carbamidocyclophane O |
|
S O |
|
( O |
|
7 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
t.s O |
|
. O |
|
] O |
|
8 O |
|
C37H54Br3NO7 O |
|
860.1382 O |
|
d O |
|
860.1378 O |
|
0.5 O |
|
95.6 O |
|
10 O |
|
OCONH2 O |
|
CH2Br O |
|
OH O |
|
CHBr2 O |
|
Carbamidocyclophane O |
|
T O |
|
( O |
|
8) O |
|
e O |
|
, O |
|
[ O |
|
t.s O |
|
. O |
|
] O |
|
|
|
9 O |
|
C37H53Br4NO7 O |
|
938.0499 O |
|
d O |
|
938.0483 O |
|
1.7 O |
|
100 O |
|
10 O |
|
OCONH2 O |
|
CHBr2 O |
|
OH O |
|
CHBr2 O |
|
Carbamidocyclophane O |
|
U O |
|
( O |
|
9 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
t.s O |
|
. O |
|
] O |
|
37 O |
|
C37H56BrNO6 O |
|
688.3207 O |
|
688.3218 O |
|
1.6 O |
|
100 O |
|
10 O |
|
OCONH2 O |
|
CH3 O |
|
H O |
|
CH2Br O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
H O |
|
CH3 O |
|
OCONH2 O |
|
CH2Br O |
|
38 O |
|
|
|
C37H53Br2NO8 O |
|
796.2059 O |
|
796.2065 O |
|
0.8 O |
|
87.6 O |
|
11 O |
|
OCONH2 O |
|
CH2OH O |
|
O O |
|
CHBr2 O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
OCONH2 O |
|
CHBrOH O |
|
O O |
|
CH2Br O |
|
O O |
|
CH2OH O |
|
OCONH2 O |
|
CHBr2 O |
|
O O |
|
CHBrOH O |
|
OCONH2 O |
|
CH2Br O |
|
3940 O |
|
C37H55Br2NO6 O |
|
766.2316 O |
|
766.2322 O |
|
766.2323 O |
|
0.9 O |
|
0.1 O |
|
85.4 O |
|
92.7 O |
|
|
|
10 O |
|
10 O |
|
OCONH2 O |
|
CH2Br O |
|
H O |
|
CH2Br O |
|
Putative O |
|
new O |
|
[7.7]paracyclophanes O |
|
f O |
|
OCONH2 O |
|
CH3 O |
|
H O |
|
CHBr2 O |
|
H O |
|
CH3 O |
|
OCONH2 O |
|
CHBr2 O |
|
41 O |
|
C37H54Br3NO6 O |
|
844.1424 O |
|
844.1428 O |
|
0.5 O |
|
97.5 O |
|
10 O |
|
OCONH2 O |
|
CH2Br O |
|
H O |
|
CHBr2 O |
|
Putative O |
|
new[7.7]paracyclophane O |
|
f O |
|
H O |
|
CH2Br O |
|
OCONH2 O |
|
CHBr2 O |
|
42 O |
|
|
|
C37H53Br4NO6 O |
|
922.0541 O |
|
922.0534 O |
|
0.8 O |
|
100 O |
|
10 O |
|
OCONH2 O |
|
CHBr2 O |
|
H O |
|
CHBr2 O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
43 O |
|
C36H55BrO6 O |
|
661.3077 O |
|
661.3109 O |
|
4.8 O |
|
79.5 O |
|
9 O |
|
OH O |
|
CH3 O |
|
OH O |
|
CH2Br O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
Chlorinated O |
|
derivatives O |
|
10 O |
|
C38H57ClN2O8 O |
|
703.3731 O |
|
703.3731 O |
|
0.0 O |
|
100 O |
|
|
|
11 O |
|
OCONH2 O |
|
CH3 O |
|
OCONH2 O |
|
CH2Cl O |
|
Carbamidocyclophane O |
|
D O |
|
( O |
|
10 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
5 O |
|
] O |
|
11 O |
|
C38H56Cl2N2O8 O |
|
737.3332 O |
|
737.3341 O |
|
1.2 O |
|
87.5 O |
|
11 O |
|
OCONH2 O |
|
CH2Cl O |
|
OCONH2 O |
|
CH2Cl O |
|
Carbamidocyclophane O |
|
J O |
|
( O |
|
11 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
7 O |
|
] O |
|
12 O |
|
C38H56Cl2N2O8 O |
|
737.3339 O |
|
737.3341 O |
|
0.3 O |
|
88.9 O |
|
11 O |
|
OCONH2 O |
|
|
|
CH3 O |
|
OCONH2 O |
|
CHCl2 O |
|
Carbamidocyclophane O |
|
C O |
|
( O |
|
12 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
5 O |
|
] O |
|
13 O |
|
C38H55Cl3N2O8 O |
|
771.2966 O |
|
771.2951 O |
|
1.9 O |
|
91.1 O |
|
11 O |
|
OCONH2 O |
|
CH2Cl O |
|
OCONH2 O |
|
CHCl2 O |
|
Carbamidocyclophane O |
|
B O |
|
( O |
|
13 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
5 O |
|
] O |
|
14 O |
|
C38H54Cl4N2O8 O |
|
805.2559 O |
|
805.2562 O |
|
0.4 O |
|
92.4 O |
|
11 O |
|
OCONH2 O |
|
|
|
CHCl2 O |
|
OCONH2 O |
|
CHCl2 O |
|
Carbamidocyclophane O |
|
A O |
|
( O |
|
14 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
5 O |
|
] O |
|
15 O |
|
C37H56ClNO7 O |
|
660.3672 O |
|
660.3673 O |
|
0.2 O |
|
96.7 O |
|
10 O |
|
OCONH2 O |
|
CH3 O |
|
OH O |
|
CH2Cl O |
|
Carbamidocyclophane O |
|
I O |
|
( O |
|
15 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
7 O |
|
] O |
|
16 O |
|
C37H55Cl2NO7 O |
|
694.3269 O |
|
694.3283 O |
|
2.0 O |
|
89.2 O |
|
10 O |
|
OCONH2 O |
|
CH3 O |
|
OH O |
|
CHCl2 O |
|
|
|
Carbamidocyclophane O |
|
K O |
|
( O |
|
16 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
7 O |
|
] O |
|
17 O |
|
C37H54Cl3NO7 O |
|
728.2903 O |
|
728.2893 O |
|
1.2 O |
|
86.4 O |
|
10 O |
|
OCONH2 O |
|
CH2Cl O |
|
OH O |
|
CHCl2 O |
|
Carbamidocyclophane O |
|
L O |
|
( O |
|
17 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
7 O |
|
] O |
|
18 O |
|
C37H53Cl4NO7 O |
|
762.2499 O |
|
762.2503 O |
|
0.5 O |
|
100 O |
|
10 O |
|
OCONH2 O |
|
CHCl2 O |
|
OH O |
|
CHCl2 O |
|
Carbamidocyclophane O |
|
F O |
|
( O |
|
18 O |
|
) O |
|
|
|
e O |
|
, O |
|
[ O |
|
6 O |
|
] O |
|
21 O |
|
C36H55ClO6 O |
|
617.3626 O |
|
617.3614 O |
|
1.9 O |
|
93.2 O |
|
9 O |
|
OH O |
|
CH3 O |
|
OH O |
|
CH2Cl O |
|
Cylindrocyclophane O |
|
A1(21 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
8 O |
|
] O |
|
22 O |
|
C36H54Cl2O6 O |
|
651.3219 O |
|
651.3225 O |
|
0.9 O |
|
80.4 O |
|
9 O |
|
OH O |
|
CH3 O |
|
OH O |
|
CHCl2 O |
|
Cylindrocyclophane O |
|
A2 O |
|
( O |
|
22 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
8 O |
|
] O |
|
23 O |
|
C36H53Cl3O6 O |
|
685.2828 O |
|
|
|
685.2835 O |
|
1.0 O |
|
84.8 O |
|
9 O |
|
OH O |
|
CH2Cl O |
|
OH O |
|
CHCl2 O |
|
Cylindrocyclophane O |
|
A3 O |
|
( O |
|
23 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
8 O |
|
] O |
|
24 O |
|
C36H52Cl4O6 O |
|
719.2434 O |
|
719.2445 O |
|
1.5 O |
|
86.9 O |
|
9 O |
|
OH O |
|
CHCl2 O |
|
OH O |
|
CHCl2 O |
|
Cylindrocyclophane O |
|
A4 O |
|
( O |
|
24 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
8 O |
|
] O |
|
31 O |
|
C36H55ClO5 O |
|
601.3665 O |
|
601.3665 O |
|
0.5 O |
|
99.3 O |
|
9 O |
|
OH O |
|
CH3 O |
|
H O |
|
|
|
CH2Cl O |
|
Cylindrocyclophane O |
|
C1 O |
|
, O |
|
[ O |
|
8 O |
|
] O |
|
32 O |
|
C36H54Cl2O5 O |
|
635.3273 O |
|
635.3276 O |
|
0.5 O |
|
95.6 O |
|
9 O |
|
OH O |
|
CH3 O |
|
H O |
|
CHCl2 O |
|
Cylindrocyclophane O |
|
C2 O |
|
, O |
|
[ O |
|
8 O |
|
] O |
|
33 O |
|
C36H53Cl3O5 O |
|
669.2898 O |
|
669.2886 O |
|
1.8 O |
|
100 O |
|
9 O |
|
OH O |
|
CH2Cl O |
|
H O |
|
CHCl2 O |
|
Cylindrocyclophane O |
|
C3 O |
|
, O |
|
[ O |
|
8 O |
|
] O |
|
34 O |
|
|
|
C36H52Cl4O5 O |
|
703.2485 O |
|
703.2496 O |
|
1.6 O |
|
100 O |
|
9 O |
|
OH O |
|
CHCl2 O |
|
H O |
|
CHCl2 O |
|
Cylindrocyclophane O |
|
C4 O |
|
, O |
|
[ O |
|
8 O |
|
] O |
|
44 O |
|
C37H56ClNO6 O |
|
644.3724 O |
|
644.3723 O |
|
0.2 O |
|
100 O |
|
10 O |
|
OCONH2 O |
|
CH3 O |
|
H O |
|
CH2Cl O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
H O |
|
CH3 O |
|
OCONH2 O |
|
CH2Cl O |
|
45 O |
|
C37H55Cl2NO7 O |
|
694.3264 O |
|
|
|
694.3283 O |
|
2.7 O |
|
84.3 O |
|
10 O |
|
OCONH2 O |
|
CH2Cl O |
|
OH O |
|
CH2Cl O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
OH O |
|
CH3 O |
|
OCONH2 O |
|
CHCl2 O |
|
46 O |
|
47 O |
|
C37H55Cl2NO6 O |
|
678.3330 O |
|
678.3332 O |
|
678.3334 O |
|
0.6 O |
|
0.3 O |
|
100 O |
|
100 O |
|
10 O |
|
10 O |
|
OCONH2 O |
|
CH2Cl O |
|
H O |
|
CH2Cl O |
|
Putative O |
|
new O |
|
[7.7]paracyclophanes O |
|
f O |
|
OCONH2 O |
|
CH3 O |
|
H O |
|
CHCl2 O |
|
|
|
H O |
|
CH3 O |
|
OCONH2 O |
|
CHCl2 O |
|
48 O |
|
C37H54Cl3NO6 O |
|
712.2952 O |
|
712.2944 O |
|
1.1 O |
|
87.1 O |
|
10 O |
|
OCONH2 O |
|
CH2Cl O |
|
H O |
|
CHCl2 O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
H O |
|
CH2Cl O |
|
OCONH2 O |
|
CHCl2 O |
|
49 O |
|
C37H53Cl4NO6 O |
|
746.2559 O |
|
746.2554 O |
|
0.3 O |
|
100 O |
|
10 O |
|
OCONH2 O |
|
CHCl2 O |
|
H O |
|
CHCl2 O |
|
Putative O |
|
new O |
|
|
|
[7.7]paracyclophane O |
|
f O |
|
50 O |
|
C36H54Cl2O6 O |
|
651.3223 O |
|
651.3225 O |
|
0.9 O |
|
79.3 O |
|
9 O |
|
OH O |
|
CH2Cl O |
|
OH O |
|
CH2Cl O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
51 O |
|
C36H54Cl2O5 O |
|
635.3275 O |
|
635.3276 O |
|
0.2 O |
|
100 O |
|
9 O |
|
H O |
|
CH3 O |
|
OH O |
|
CHCl2 O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
OH O |
|
CH2Cl O |
|
H O |
|
CH2Cl O |
|
52 O |
|
|
|
C36H54Cl2O4 O |
|
619.3323 O |
|
619.3326 O |
|
0.5 O |
|
100 O |
|
9 O |
|
H O |
|
CH2Cl O |
|
H O |
|
CH2Cl O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
H O |
|
CH3 O |
|
H O |
|
CHCl2 O |
|
Non-halogenated O |
|
derivatives O |
|
19 O |
|
C38H58N2O8 O |
|
669.4122 O |
|
669.412 O |
|
0.3 O |
|
100 O |
|
11 O |
|
OCONH2 O |
|
CH3 O |
|
OCONH2 O |
|
CH3 O |
|
Carbamidocyclophane O |
|
E O |
|
( O |
|
19 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
5 O |
|
] O |
|
20 O |
|
C37H57NO7 O |
|
|
|
626.4064 O |
|
626.4062 O |
|
0.3 O |
|
100 O |
|
10 O |
|
OCONH2 O |
|
CH3 O |
|
OH O |
|
CH3 O |
|
Carbamidocyclophane O |
|
H O |
|
( O |
|
20 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
7 O |
|
] O |
|
25 O |
|
C36H56O6 O |
|
583.3994 O |
|
583.4004 O |
|
1.7 O |
|
83.1 O |
|
9 O |
|
OH O |
|
CH3 O |
|
OH O |
|
CH3 O |
|
Cylindrocyclophane O |
|
A O |
|
( O |
|
25 O |
|
) O |
|
e O |
|
, O |
|
[ O |
|
4 O |
|
] O |
|
35 O |
|
C36H56O5 O |
|
567.4004 O |
|
567.4055 O |
|
2.3 O |
|
89.7 O |
|
9 O |
|
OH O |
|
CH3 O |
|
H O |
|
CH3 O |
|
|
|
Cylindrocyclophane O |
|
C O |
|
, O |
|
[ O |
|
9 O |
|
] O |
|
36 O |
|
C36H56O4 O |
|
551.4102 O |
|
551.4106 O |
|
0.7 O |
|
100 O |
|
9 O |
|
H O |
|
CH3 O |
|
H O |
|
CH3 O |
|
Cylindrocyclophane O |
|
F O |
|
, O |
|
[ O |
|
9 O |
|
] O |
|
53 O |
|
C37H55NO7 O |
|
624.3888 O |
|
624.3906 O |
|
2.9 O |
|
88.7 O |
|
11 O |
|
OCONH2 O |
|
CH3 O |
|
O O |
|
CH3 O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
54 O |
|
C37H57NO6 O |
|
610.4113 O |
|
610.4113 O |
|
0.0 O |
|
100 O |
|
10 O |
|
|
|
OCONH2 O |
|
CH3 O |
|
H O |
|
CH3 O |
|
Putative O |
|
new O |
|
[7.7]paracyclophane O |
|
f O |
|
a O |
|
Abbreviations O |
|
: O |
|
Meas O |
|
. O |
|
|
|
Genome O |
|
mining O |
|
for O |
|
orthologs O |
|
of O |
|
LtnJ O |
|
uncovered O |
|
three O |
|
other O |
|
putative O |
|
dehydrogenases;421 O |
|
SacJ O |
|
, O |
|
which O |
|
is O |
|
located O |
|
in O |
|
the O |
|
Staphylococcus O |
|
aureus O |
|
C55 O |
|
operon O |
|
for O |
|
the O |
|
biosynthesis O |
|
of O |
|
staphylococcin O |
|
C55,427 O |
|
a O |
|
lanthipeptide O |
|
predicted O |
|
to O |
|
be O |
|
very O |
|
similar O |
|
in O |
|
structure O |
|
to O |
|
lacticin O |
|
3147 O |
|
; O |
|
PenN O |
|
from O |
|
Pediococcus O |
|
pentosaceus O |
|
FBB61 O |
|
, O |
|
which O |
|
is O |
|
required O |
|
to O |
|
access O |
|
bioactive O |
|
pediocin O |
|
A;428 O |
|
and O |
|
NpnJ O |
|
( O |
|
originally O |
|
named O |
|
|
|
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|
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|
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|
from O |
|
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|
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|
Nostoc O |
|
punctiforme O |
|
PCC73102 O |
|
cluster O |
|
that O |
|
contains O |
|
a O |
|
LanM O |
|
but O |
|
does O |
|
not O |
|
produce O |
|
lanthipeptides O |
|
as O |
|
the O |
|
precursor O |
|
peptides O |
|
( O |
|
NpnA O |
|
) O |
|
do O |
|
not O |
|
contain O |
|
cysteines.368 O |
|
LtnJ O |
|
, O |
|
NpnJ O |
|
, O |
|
PenN O |
|
, O |
|
and O |
|
SacJ O |
|
share O |
|
many O |
|
conserved O |
|
residues O |
|
including O |
|
three O |
|
or O |
|
four O |
|
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|
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|
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|
predicted O |
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|
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|
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|
( O |
|
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|
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|
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|
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|
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|
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|
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|
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|
LtnJ O |
|
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|
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|
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|
and O |
|
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|
|
|
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|
all O |
|
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|
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|
four O |
|
enzymes O |
|
have O |
|
been O |
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|
as O |
|
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|
dehydrogenases O |
|
based O |
|
on O |
|
their O |
|
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|
and O |
|
NADPH-dependence.425 O |
|
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|
dehydrogenase O |
|
activity O |
|
for O |
|
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|
and O |
|
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|
was O |
|
demonstrated O |
|
in O |
|
vivo O |
|
with O |
|
the O |
|
lacticin O |
|
3147 O |
|
substrate O |
|
, O |
|
confirming O |
|
their O |
|
function O |
|
and O |
|
suggesting O |
|
that O |
|
these O |
|
enzymes O |
|
do O |
|
not O |
|
require O |
|
a O |
|
leader O |
|
peptide O |
|
as O |
|
a O |
|
non-native O |
|
substrate O |
|
was O |
|
accepted.429 O |
|
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|
, O |
|
supplementing O |
|
the O |
|
ΔltnJ O |
|
strain O |
|
described O |
|
above O |
|
with O |
|
penN O |
|
restored O |
|
d-Ala O |
|
formation O |
|
in O |
|
both O |
|
Ltnα O |
|
and O |
|
Ltnβ O |
|
, O |
|
whereas O |
|
supplementation O |
|
with O |
|
|
|
sacJ O |
|
restored O |
|
d-Ala O |
|
formation O |
|
in O |
|
Ltnα O |
|
but O |
|
not O |
|
in O |
|
Ltnβ O |
|
. O |
|
|
|
The O |
|
whole O |
|
DNA O |
|
sequence O |
|
of O |
|
the O |
|
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|
venezuelae O |
|
genome O |
|
was O |
|
determined O |
|
, O |
|
including O |
|
the O |
|
chloramphenicol O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
[ O |
|
420 O |
|
] O |
|
( O |
|
GB O |
|
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|
FR845719 B-bgc-accession |
|
and O |
|
AF262220 B-bgc-accession |
|
) O |
|
. O |
|
|
|
Two O |
|
putative O |
|
halogenase O |
|
genes O |
|
, O |
|
mymM O |
|
and O |
|
mymP O |
|
, O |
|
were O |
|
found O |
|
in O |
|
S. O |
|
olivaceus O |
|
FXJ8.012Δ1741 O |
|
, O |
|
while O |
|
only O |
|
one O |
|
candidate O |
|
, O |
|
myeP O |
|
, O |
|
was O |
|
present O |
|
in O |
|
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|
sp. O |
|
FXJ1.235 O |
|
. O |
|
|
|
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|
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|
ast O |
|
cluster O |
|
, O |
|
where O |
|
there O |
|
are O |
|
multiple O |
|
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|
enzymes O |
|
encoded O |
|
( O |
|
one O |
|
terpene O |
|
synthase O |
|
and O |
|
two O |
|
phosphatases O |
|
) O |
|
, O |
|
the O |
|
putative O |
|
nanangenine O |
|
cluster O |
|
only O |
|
encodes O |
|
one O |
|
such O |
|
enzyme O |
|
, O |
|
FE257_006542 O |
|
. O |
|
|
|
Results O |
|
and O |
|
discussion O |
|
Biosynthetic O |
|
origin O |
|
of O |
|
the O |
|
polycyclic O |
|
scaffold O |
|
of O |
|
TXNs O |
|
TXN-A O |
|
was O |
|
originally O |
|
isolated O |
|
from O |
|
S. O |
|
bottropensis O |
|
DO-45 O |
|
with O |
|
the O |
|
isolation O |
|
of O |
|
20 O |
|
mg O |
|
from O |
|
an O |
|
18 O |
|
L O |
|
fermentation O |
|
broth;1,2 O |
|
however O |
|
this O |
|
titer O |
|
was O |
|
not O |
|
efficient O |
|
enough O |
|
for O |
|
biosynthetic O |
|
studies O |
|
. O |
|
|
|
Swainsonine O |
|
is O |
|
an O |
|
indolizidine O |
|
alkaloid O |
|
that O |
|
is O |
|
produced O |
|
by O |
|
insect O |
|
and O |
|
plant O |
|
pathogens O |
|
and O |
|
symbionts O |
|
belonging O |
|
to O |
|
the O |
|
order O |
|
Hypocreales O |
|
, O |
|
Chaetothyriales O |
|
, O |
|
Onygenales O |
|
, O |
|
Pleosporales O |
|
, O |
|
and O |
|
Leotiomycetes O |
|
. O |
|
|
|
The O |
|
cluster O |
|
houses O |
|
genes O |
|
for O |
|
3-hydroxybutyryl-CoA O |
|
dehydrogenase O |
|
( O |
|
tueI O |
|
) O |
|
and O |
|
for O |
|
a O |
|
carboxylating O |
|
enoyl-thioester O |
|
reductase O |
|
( O |
|
tueH O |
|
) O |
|
bolstering O |
|
the O |
|
identification O |
|
of O |
|
the O |
|
cluster O |
|
as O |
|
governing O |
|
production O |
|
of O |
|
a O |
|
butyrate O |
|
unit-containing O |
|
polyketide.38 O |
|
|
|
The O |
|
suitability O |
|
of O |
|
our O |
|
primer O |
|
set O |
|
to O |
|
detect O |
|
phenazine O |
|
genes O |
|
in O |
|
Pseudomonas O |
|
species O |
|
was O |
|
further O |
|
demonstrated O |
|
by O |
|
performing O |
|
a O |
|
database O |
|
search O |
|
that O |
|
matched O |
|
perfectly O |
|
several O |
|
phenazine O |
|
genes O |
|
, O |
|
e.g. O |
|
, O |
|
P. O |
|
chlororaphis O |
|
( O |
|
L48339 B-bgc-accession |
|
) O |
|
, O |
|
Pseudomonas O |
|
sp. O |
|
M18 O |
|
( O |
|
FJ494909 B-bgc-accession |
|
) O |
|
, O |
|
P. O |
|
aeruginosa O |
|
( O |
|
FM209186 B-bgc-accession |
|
, O |
|
CP000744 B-bgc-accession |
|
, O |
|
CP000438 B-bgc-accession |
|
, O |
|
AE004091 B-bgc-accession |
|
, O |
|
AF005404 B-bgc-accession |
|
) O |
|
. O |
|
|
|
Different O |
|
phycotoxins O |
|
cause O |
|
distinct O |
|
poisoning O |
|
events O |
|
. O |
|
|
|
Results O |
|
and O |
|
Discussion O |
|
Identification O |
|
of O |
|
the O |
|
Conglobatin O |
|
Biosynthetic O |
|
Gene O |
|
Cluster O |
|
Conglobatin O |
|
is O |
|
a O |
|
symmetrical O |
|
polyketide O |
|
macrodiolide O |
|
, O |
|
and O |
|
inspection O |
|
of O |
|
its O |
|
structure O |
|
suggests O |
|
that O |
|
its O |
|
assembly O |
|
is O |
|
governed O |
|
by O |
|
an O |
|
NRPS/PKS O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
. O |
|
|
|
= O |
|
Epichloë O |
|
canadensis O |
|
, O |
|
FaTG-2 O |
|
= O |
|
Neotyphodium O |
|
species O |
|
FaTG-2 O |
|
, O |
|
N. O |
|
chi O |
|
= O |
|
Neotyphodium O |
|
chisosum O |
|
, O |
|
N. O |
|
coe O |
|
. O |
|
|
|
Ouabain O |
|
and O |
|
digoxin O |
|
are O |
|
the O |
|
typical O |
|
endogenous O |
|
cardiac O |
|
glycosides O |
|
. O |
|
|
|
Phylogeny O |
|
of O |
|
three O |
|
LOL O |
|
genes O |
|
, O |
|
lolC O |
|
, O |
|
lolN O |
|
, O |
|
and O |
|
lolP. O |
|
Pseudogenes O |
|
of O |
|
lolC O |
|
and O |
|
lolP O |
|
are O |
|
labeled O |
|
lolCψ O |
|
and O |
|
lolPψ O |
|
, O |
|
respectively O |
|
. O |
|
|
|
The O |
|
leader O |
|
sequence O |
|
is O |
|
removed O |
|
during O |
|
the O |
|
transport O |
|
out O |
|
of O |
|
the O |
|
cell O |
|
by O |
|
the O |
|
bifunctional O |
|
enzyme O |
|
LanT O |
|
( O |
|
transporter O |
|
with O |
|
N-terminal O |
|
protease O |
|
) O |
|
[31].Table O |
|
3 O |
|
Detected O |
|
putative O |
|
lanthipeptide O |
|
gene O |
|
clusters O |
|
PhylumLanthipeptide O |
|
classLocus O |
|
tag O |
|
of O |
|
the O |
|
lanthipeptide O |
|
modifying O |
|
enzyme O |
|
LanSimilar O |
|
to O |
|
† O |
|
Reference O |
|
# O |
|
Clostridium O |
|
cellulovorans O |
|
743B O |
|
, O |
|
ATCC O |
|
35296FirmicutesI O |
|
Clocel_4251 O |
|
Clocel_4256 O |
|
Clocel_4262 O |
|
Clostridium O |
|
kluyveri O |
|
DSM O |
|
|
|
555FirmicutesI O |
|
CKL_3505 O |
|
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longum O |
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|
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acetobutylicum O |
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|
824FimicutesII O |
|
CA_C0082 O |
|
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|
acetobutylicum O |
|
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|
1731FimicutesII O |
|
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|
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|
acetobutylicum O |
|
EA O |
|
2018FimicutesII O |
|
CEA_G0073 O |
|
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|
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|
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|
|
|
8052FimicutesII O |
|
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|
[ O |
|
25 O |
|
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|
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|
botulinum O |
|
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|
065FimicutesII O |
|
H04402_00616 O |
|
H04402_00617 O |
|
lichenicidin O |
|
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|
cellulovorans O |
|
743B O |
|
, O |
|
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|
35296FimicutesII O |
|
Clocel_0875 O |
|
lichenicidin[32]II O |
|
Clocel O |
|
_ O |
|
4225 O |
|
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|
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|
lactoaceticus O |
|
6A O |
|
, O |
|
DSM O |
|
|
|
9545FimicutesII O |
|
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|
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|
bescii O |
|
Z-1320 O |
|
, O |
|
DSM O |
|
6725FimicutesII O |
|
Athe_1107 O |
|
lichenicidin[32 O |
|
] O |
|
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|
kristjanssonii O |
|
177R1B O |
|
, O |
|
DSM O |
|
12137FimicutesII O |
|
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|
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|
longum O |
|
infantis O |
|
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|
1222 O |
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|
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|
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|
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|
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acnes O |
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
funkii O |
|
e4096 O |
|
[ O |
|
28 O |
|
] O |
|
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|
robustum O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
|
|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
species O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
presence O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
pathway O |
|
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|
|
|
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|
Size O |
|
( O |
|
bp/aa O |
|
) O |
|
Proposed O |
|
Function O |
|
Orthologue O |
|
identified O |
|
by O |
|
BLASTP O |
|
search O |
|
Identity/Similarity O |
|
[ O |
|
% O |
|
] O |
|
orf1 O |
|
1638/545 O |
|
ATPase O |
|
SZN_31494 O |
|
, O |
|
Streptomyces O |
|
zinciresistens O |
|
85/89 O |
|
mpz1 O |
|
486/161 O |
|
Phenazine O |
|
biosynthesis O |
|
protein O |
|
PhzB O |
|
, O |
|
Pseudomonas O |
|
fluorescens O |
|
69/81 O |
|
mpz2 O |
|
1224/407 O |
|
3-Deoxy-D-arabino-heptulosonate O |
|
7-phosphate O |
|
synthase O |
|
PhzC O |
|
, O |
|
|
|
Pseudomonas O |
|
fluorescens O |
|
49/61 O |
|
mpz3 O |
|
573/190 O |
|
2,3-Dihydro-3-hydroxy-anthranilate O |
|
synthase O |
|
PhzD O |
|
, O |
|
Pseudomonas O |
|
fluorescens O |
|
56/73 O |
|
mpz4 O |
|
1941/646 O |
|
2-Amino-2-desoxy-isochorismate O |
|
synthase O |
|
PhzE O |
|
, O |
|
Pseudomonas O |
|
fluorescens O |
|
54/69 O |
|
mpz5 O |
|
1167/388 O |
|
trans-2,3-Dihydro-3-hydroxyanthranilate O |
|
isomerase O |
|
|
|
PhzF O |
|
, O |
|
Pseudomonas O |
|
fluorescens O |
|
60/70 O |
|
mpz6 O |
|
636/211 O |
|
FMN-dependent O |
|
oxidase O |
|
PhzG O |
|
, O |
|
Pseudomonas O |
|
fluorescens O |
|
48/65 O |
|
mpz7 O |
|
1623/540 O |
|
Monooxygenase O |
|
ChnB O |
|
, O |
|
Brachymonas O |
|
petroleovorans O |
|
56/74 O |
|
mpz8 O |
|
330/109 O |
|
Monooxygenase O |
|
TcmH O |
|
, O |
|
Streptomyces O |
|
glaucescens O |
|
48/60 O |
|
mpz9 O |
|
1215/404 O |
|
Flavin O |
|
dependent O |
|
hydroxylase O |
|
PhzS O |
|
, O |
|
Pseudomonas O |
|
|
|
aeruginosa O |
|
51/62 O |
|
mpz10 O |
|
996/331 O |
|
Prenyltransferase O |
|
O3I_007965 O |
|
, O |
|
Nocardia O |
|
brasiliensis O |
|
ATCC O |
|
700358 O |
|
33/51 O |
|
mpz11 O |
|
1020/339 O |
|
Mevalonate O |
|
kinase O |
|
MK O |
|
, O |
|
Streptomyces O |
|
cinnamonensis O |
|
57/71 O |
|
mpz12 O |
|
1044/347 O |
|
Mevalonate O |
|
diphosphate O |
|
decarboxylase O |
|
Mcl8 O |
|
, O |
|
Streptomyces O |
|
sp. O |
|
CNH189 O |
|
73/80 O |
|
mpz13 O |
|
1140/379 O |
|
|
|
Phosphomevalonate O |
|
kinase O |
|
PMK O |
|
, O |
|
Streptomyces O |
|
sp. O |
|
KO-3988 O |
|
57/70 O |
|
mpz14 O |
|
1092/363 O |
|
Isopentenyl O |
|
diphosphate O |
|
isomerase O |
|
Mcl6 O |
|
, O |
|
Streptomyces O |
|
sp. O |
|
CNH189 O |
|
74/86 O |
|
mpz15 O |
|
1068/355 O |
|
3-Hydroxy-3-methylglutaryl O |
|
CoA O |
|
reductase O |
|
HMGR O |
|
, O |
|
Streptomyces O |
|
anulatus O |
|
80/89 O |
|
mpz16 O |
|
1185/394 O |
|
|
|
3-Hydroxy-3-methylglutaryl O |
|
CoA O |
|
synthase O |
|
Mcl4 O |
|
, O |
|
Streptomyces O |
|
sp. O |
|
CNH189 O |
|
76/87 O |
|
orf18 O |
|
1212/403 O |
|
integrase O |
|
catalytic O |
|
subunit O |
|
OCO_06920 O |
|
, O |
|
Mycobacterium O |
|
intracellulare O |
|
MOTT-02 O |
|
48/63 O |
|
The O |
|
six O |
|
genes O |
|
mpz11 O |
|
- O |
|
16 O |
|
show O |
|
obvious O |
|
similarity O |
|
( O |
|
89 O |
|
- O |
|
70 O |
|
% O |
|
) O |
|
to O |
|
genes O |
|
coding O |
|
for O |
|
enzymes O |
|
of O |
|
the O |
|
mevalonate O |
|
pathway O |
|
, O |
|
corresponding O |
|
to O |
|
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|
fact O |
|
that O |
|
the O |
|
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|
moieties O |
|
of O |
|
|
|
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|
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|
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|
, O |
|
and O |
|
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|
originate O |
|
from O |
|
the O |
|
mevalonate O |
|
pathway O |
|
[ O |
|
14 O |
|
] O |
|
. O |
|
|
|
Two O |
|
members O |
|
of O |
|
the O |
|
mmpL O |
|
family O |
|
, O |
|
a O |
|
group O |
|
of O |
|
genes O |
|
encoding O |
|
large O |
|
membrane O |
|
proteins O |
|
, O |
|
are O |
|
also O |
|
required O |
|
for O |
|
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|
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|
[ O |
|
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|
] O |
|
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|
|
|
In O |
|
general O |
|
, O |
|
the O |
|
four O |
|
tested O |
|
recombinant O |
|
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|
domains O |
|
were O |
|
found O |
|
to O |
|
activate O |
|
selectively O |
|
predicted O |
|
amino O |
|
acids O |
|
, O |
|
experimentally O |
|
confirming O |
|
the O |
|
speculation O |
|
that O |
|
the O |
|
plp O |
|
gene O |
|
cluster O |
|
involved O |
|
in O |
|
pelgipeptin O |
|
biosynthesis O |
|
. O |
|
|
|
Anti-SMASH O |
|
software13 O |
|
identified O |
|
two O |
|
potential O |
|
PKS-encoding O |
|
BGCs O |
|
in O |
|
each O |
|
genome O |
|
( O |
|
Supplementary O |
|
Figure O |
|
O O |
|
6 O |
|
) O |
|
|
|
Viomycin O |
|
and O |
|
capreomycin O |
|
are O |
|
tuberactinomycin O |
|
group O |
|
antibiotics O |
|
used O |
|
for O |
|
the O |
|
treatment O |
|
of O |
|
multi-resistant O |
|
tuberculosis O |
|
. O |
|
|
|
Examination O |
|
of O |
|
the O |
|
resultant O |
|
strain O |
|
revealed O |
|
that O |
|
the O |
|
L. O |
|
innocua O |
|
LIPI-3 O |
|
is O |
|
indeed O |
|
functional O |
|
as O |
|
evidenced O |
|
by O |
|
a O |
|
clear O |
|
haemolytic O |
|
phenotype O |
|
on O |
|
Columbia O |
|
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|
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|
|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
|
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|
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|
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|
|
|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
efficiently.196 O |
|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
differences O |
|
in O |
|
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|
acceptor O |
|
stem O |
|
. O |
|
|
|
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|
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|
an O |
|
anthracycline O |
|
group O |
|
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|
produced O |
|
by O |
|
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|
nogalater O |
|
. O |
|
|
|
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|
of O |
|
the O |
|
reverse O |
|
transcription O |
|
of O |
|
phtL O |
|
, O |
|
the O |
|
intergenic O |
|
region O |
|
of O |
|
phtMN O |
|
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|
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|
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|
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|
that O |
|
expression O |
|
of O |
|
these O |
|
genes O |
|
in O |
|
enhanced O |
|
by O |
|
components O |
|
present O |
|
in O |
|
leaf O |
|
extracts O |
|
. O |
|
|
|
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|
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|
of O |
|
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|
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|
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|
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|
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|
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|
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|
fluorescens O |
|
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|
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|
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|
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|
at O |
|
the O |
|
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|
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|
( O |
|
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|
, O |
|
UK O |
|
) O |
|
using O |
|
the O |
|
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|
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|
( O |
|
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|
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|
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|
platform O |
|
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|
and O |
|
assembly O |
|
using O |
|
the O |
|
HGAP2 O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
and O |
|
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|
to O |
|
PC-19 O |
|
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|
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|
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|
genes O |
|
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|
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|
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|
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|
|
|
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|
synthase O |
|
domains O |
|
are O |
|
as O |
|
follows O |
|
KS O |
|
ketosynthase O |
|
, O |
|
AT O |
|
acyltransferase O |
|
, O |
|
KR O |
|
ketoreductase O |
|
, O |
|
DH O |
|
dehydratase O |
|
, O |
|
ACP O |
|
acyl-carrier-protein O |
|
, O |
|
CAL O |
|
CoA O |
|
ligase O |
|
, O |
|
KSIII O |
|
3-oxoacyl-ACP O |
|
synthase O |
|
III O |
|
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|
regulation O |
|
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|
ORFs O |
|
( O |
|
gonMR O |
|
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|
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|
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|
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|
and O |
|
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|
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|
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|
be O |
|
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|
for O |
|
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|
pathway O |
|
regulation O |
|
as O |
|
they O |
|
code O |
|
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|
proteins O |
|
with O |
|
|
|
high O |
|
sequence O |
|
resemblance O |
|
to O |
|
transcription O |
|
regulatory O |
|
proteins O |
|
. O |
|
|
|
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|
of O |
|
ergot O |
|
alkaloids O |
|
goes O |
|
via O |
|
the O |
|
common O |
|
intermediate O |
|
chanoclavine-I O |
|
, O |
|
and O |
|
studies O |
|
of O |
|
the O |
|
key O |
|
enzymes O |
|
, O |
|
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|
and O |
|
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|
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|
involved O |
|
in O |
|
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|
formation O |
|
, O |
|
have O |
|
relied O |
|
on O |
|
gene O |
|
complementation O |
|
in O |
|
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|
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|
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|
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|
characterization O |
|
has O |
|
been O |
|
hampered O |
|
by O |
|
difficulties O |
|
of O |
|
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|
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|
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|
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|
. O |
|
|
|
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|
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|
gene O |
|
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|
a O |
|
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|
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|
and O |
|
C O |
|
precursor O |
|
peptide O |
|
of O |
|
71 O |
|
amino O |
|
acid O |
|
residues O |
|
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|
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|
first O |
|
37 O |
|
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|
which O |
|
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|
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|
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|
leader O |
|
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|
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|
processing O |
|
. O |
|
|
|
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|
genes O |
|
are O |
|
indicated O |
|
with O |
|
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|
numbers O |
|
as O |
|
shown O |
|
in O |
|
Table O |
|
5Table O |
|
5Putative O |
|
hyaluromycin O |
|
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|
gene O |
|
cluster O |
|
and O |
|
the O |
|
neighboring O |
|
genesOrf1-Size O |
|
(aa)Proposed O |
|
functionClosest O |
|
homologHomolog O |
|
( O |
|
I/S O |
|
, O |
|
% O |
|
) O |
|
inDescription O |
|
, O |
|
Origin O |
|
, O |
|
Accession O |
|
numberI/Sb O |
|
(%)grh O |
|
clusterrub O |
|
cluster769230cyclasehypothetical O |
|
protein O |
|
, O |
|
Streptomyces O |
|
fulvoviolaceus O |
|
, O |
|
|
|
WP_05242508254/63–RubK O |
|
(53/63)768a656ABC O |
|
transporter O |
|
ATP-binding O |
|
proteinmultidrug O |
|
ABC O |
|
transporter O |
|
ATP-binding O |
|
protein O |
|
, O |
|
Actinopolymorpha O |
|
alba O |
|
, O |
|
WP_02057673170/83––767a577multidrug O |
|
ABC O |
|
transporter O |
|
ATPasemultidrug O |
|
ABC O |
|
transporter O |
|
ATPase O |
|
, O |
|
Streptomyces O |
|
varsoviensis O |
|
, O |
|
|
|
WP_03088138569/81––766a117MarR O |
|
family O |
|
transcriptional O |
|
regulatorMarR O |
|
family O |
|
transcriptional O |
|
regulator O |
|
, O |
|
Actinomadura O |
|
macra O |
|
, O |
|
WP_06746891145/63––765a72unknownhypothetical O |
|
protein O |
|
, O |
|
Streptomyces O |
|
aurantiacus O |
|
, O |
|
WP_055507532.56/60––764a498transcriptional O |
|
regulatorhypothetical O |
|
protein O |
|
, O |
|
Streptomyces O |
|
sp. O |
|
NRRL O |
|
WC-3742 O |
|
, O |
|
|
|
WP_05183632055/63GrhR2 O |
|
(34/48)763a533amide O |
|
synthetasehypothetical O |
|
protein O |
|
, O |
|
partial O |
|
, O |
|
Streptomyces O |
|
sp. O |
|
NRRL O |
|
WC-3742 O |
|
, O |
|
WP_07891086060/70––762a4055-aminolevulinate O |
|
synthaseAsuD2 O |
|
, O |
|
Streptomyces O |
|
nodosus O |
|
subsp O |
|
. O |
|
|
|
These O |
|
results O |
|
confirmed O |
|
that O |
|
MyeD O |
|
and O |
|
MyeG O |
|
were O |
|
essential O |
|
for O |
|
mycemycin O |
|
biosynthesis O |
|
and O |
|
MyeP O |
|
was O |
|
responsible O |
|
for O |
|
the O |
|
post-halogenation O |
|
of O |
|
mycemycin O |
|
in O |
|
S. O |
|
sp. O |
|
FXJ1.235 O |
|
. O |
|
|
|
Lantibiotic O |
|
gene O |
|
clusters O |
|
identified O |
|
in O |
|
firmicutes O |
|
Identification O |
|
of O |
|
novel O |
|
Bacillus O |
|
cereus O |
|
associated O |
|
lantibiotic O |
|
clusters O |
|
Bacillus O |
|
species O |
|
are O |
|
rod-shaped O |
|
, O |
|
endospore-forming O |
|
aerobic O |
|
or O |
|
facultatively O |
|
anaerobic O |
|
, O |
|
Gram-positive O |
|
bacteria O |
|
that O |
|
are O |
|
ubiquitous O |
|
in O |
|
nature O |
|
. O |
|
|
|
Elucidation O |
|
of O |
|
Final O |
|
Steps O |
|
of O |
|
the O |
|
Marineosins O |
|
Biosynthetic O |
|
Pathway O |
|
through O |
|
Identification O |
|
and O |
|
Characterization O |
|
of O |
|
the O |
|
Corresponding O |
|
Gene O |
|
Cluster O |
|
O O |
|
The O |
|
marine O |
|
Streptomyces O |
|
sp. O |
|
CNQ-617 O |
|
produces O |
|
two O |
|
diastereomers O |
|
, O |
|
marineosins O |
|
A O |
|
and O |
|
B. O |
|
These O |
|
are O |
|
structurally O |
|
related O |
|
to O |
|
alkyl O |
|
prodiginines O |
|
, O |
|
but O |
|
with O |
|
a O |
|
more O |
|
complex O |
|
cyclization O |
|
and O |
|
an O |
|
unusual O |
|
spiroaminal O |
|
skeleton O |
|
|
|
Tetrodotoxin O |
|
is O |
|
known O |
|
to O |
|
be O |
|
biosynthesized O |
|
by O |
|
various O |
|
bacteria O |
|
, O |
|
including O |
|
actinobacteria O |
|
, O |
|
bacteroides O |
|
, O |
|
firmicutes O |
|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
gene O |
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|
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|
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|
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|
1990 O |
|
and O |
|
were O |
|
continuously O |
|
optimized O |
|
by O |
|
conventional O |
|
mutagenesis O |
|
and O |
|
screening O |
|
experiments O |
|
. O |
|
|
|
The O |
|
Role O |
|
of O |
|
Each O |
|
Gene O |
|
within O |
|
the O |
|
fus O |
|
Gene O |
|
Cluster O |
|
in O |
|
Inhibition O |
|
of O |
|
F. O |
|
oxysporum O |
|
f. O |
|
sp. O |
|
cucumerium O |
|
|
|
Results O |
|
Distribution O |
|
of O |
|
the O |
|
anabaenopeptin O |
|
synthesis O |
|
genes O |
|
among O |
|
the O |
|
genus O |
|
planktothrix O |
|
Phylogenetic O |
|
analysis O |
|
of O |
|
all O |
|
125 O |
|
Planktothrix O |
|
strains O |
|
revealed O |
|
a O |
|
diversification O |
|
comprising O |
|
three O |
|
major O |
|
lineages O |
|
: O |
|
Lineage O |
|
1 O |
|
and O |
|
Lineage O |
|
2 O |
|
represented O |
|
only O |
|
the O |
|
strains O |
|
assigned O |
|
to O |
|
P. O |
|
agardhii/P. O |
|
rubescens O |
|
and O |
|
Lineage O |
|
3 O |
|
represented O |
|
P. O |
|
pseudagardhii O |
|
, O |
|
P. O |
|
mougeotii O |
|
, O |
|
and O |
|
P. O |
|
tepida O |
|
( O |
|
Figure O |
|
2 O |
|
) O |
|
. O |
|
|
|
Results O |
|
and O |
|
discussion O |
|
General O |
|
features O |
|
of O |
|
anaerobe O |
|
genomes O |
|
with O |
|
respect O |
|
to O |
|
RiPPs O |
|
To O |
|
survey O |
|
the O |
|
diversity O |
|
of O |
|
RiPPs O |
|
we O |
|
have O |
|
undertaken O |
|
a O |
|
bioinformatic O |
|
investigation O |
|
of O |
|
211 O |
|
complete O |
|
and O |
|
published O |
|
anaerobe O |
|
genomes O |
|
for O |
|
the O |
|
presence O |
|
of O |
|
RiPP O |
|
genes O |
|
and O |
|
gene O |
|
clusters O |
|
. O |
|
|
|
We O |
|
therefore O |
|
assumed O |
|
that O |
|
proteins O |
|
Au8003 O |
|
and O |
|
Au11565 O |
|
were O |
|
sesterterpene O |
|
synthase O |
|
, O |
|
and O |
|
that O |
|
Au13192 O |
|
was O |
|
diterpene O |
|
synthase O |
|
. O |
|
|
|
The O |
|
acn O |
|
cluster O |
|
localized O |
|
to O |
|
a O |
|
39.8 O |
|
kb O |
|
length O |
|
region O |
|
consisting O |
|
of O |
|
25 O |
|
open O |
|
reading O |
|
frames O |
|
( O |
|
ORFs O |
|
) O |
|
, O |
|
including O |
|
a O |
|
set O |
|
of O |
|
four O |
|
genes O |
|
that O |
|
drive O |
|
the O |
|
construction O |
|
of O |
|
the O |
|
4-methyl-3-hydroxy-anthranilic O |
|
acid O |
|
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|
4-MHA O |
|
) O |
|
precursor O |
|
and O |
|
three O |
|
non-ribosomal O |
|
peptide O |
|
synthetases O |
|
( O |
|
NRPSs O |
|
) O |
|
that O |
|
generate O |
|
the O |
|
4-MHA O |
|
pentapeptide O |
|
semi-lactone O |
|
, O |
|
which O |
|
, O |
|
upon O |
|
dimerization O |
|
, O |
|
affords O |
|
final O |
|
actinomycin O |
|
D. O |
|
Furthermore O |
|
, O |
|
the O |
|
acn O |
|
cluster O |
|
contains O |
|
four O |
|
positive O |
|
regulatory O |
|
genes O |
|
|
|
acnWU4RO O |
|
, O |
|
which O |
|
were O |
|
identified O |
|
by O |
|
in O |
|
vivo O |
|
gene O |
|
inactivation O |
|
studies O |
|
. O |
|
|
|
Discovery O |
|
and O |
|
Biosynthesis O |
|
of O |
|
the O |
|
Antibiotic O |
|
Bicyclomycin O |
|
in O |
|
Distantly O |
|
Related O |
|
Bacterial O |
|
Classes O |
|
ABSTRACT O |
|
Bicyclomycin O |
|
( O |
|
BCM O |
|
) O |
|
is O |
|
a O |
|
clinically O |
|
promising O |
|
antibiotic O |
|
that O |
|
is O |
|
biosynthesized O |
|
by O |
|
Streptomyces O |
|
cinnamoneus O |
|
DSM O |
|
41675 O |
|
. O |
|
|
|
Further O |
|
mutation O |
|
analysis O |
|
revealed O |
|
that O |
|
with O |
|
the O |
|
exception O |
|
of O |
|
fusTE O |
|
, O |
|
the O |
|
seven O |
|
genes O |
|
fusG O |
|
, O |
|
fusF O |
|
, O |
|
fusE O |
|
, O |
|
fusD O |
|
, O |
|
fusC O |
|
, O |
|
fusB O |
|
, O |
|
and O |
|
fusA O |
|
within O |
|
the O |
|
fus O |
|
cluster O |
|
were O |
|
all O |
|
involved O |
|
in O |
|
inhibiting O |
|
fungi O |
|
. O |
|
|
|
( O |
|
ii O |
|
) O |
|
EPS273-B O |
|
belongs O |
|
to O |
|
P-loop_NTPase O |
|
superfamily O |
|
and O |
|
is O |
|
predicted O |
|
to O |
|
be O |
|
a O |
|
sensor O |
|
kinase O |
|
. O |
|
|
|
The O |
|
analysis O |
|
of O |
|
the O |
|
genome O |
|
using O |
|
antiSMASH O |
|
software O |
|
revealed O |
|
that O |
|
29 O |
|
gene O |
|
clusters O |
|
are O |
|
involved O |
|
in O |
|
the O |
|
biosynthesis O |
|
of O |
|
diverse O |
|
secondary O |
|
metabolites O |
|
including O |
|
terpenes O |
|
, O |
|
lanthipeptides O |
|
, O |
|
non-ribosomal O |
|
peptides O |
|
, O |
|
and O |
|
polyketides O |
|
( O |
|
Supplementary O |
|
Table O |
|
S2 O |
|
) O |
|
. O |
|
|
|
Their O |
|
inhibitory O |
|
activities O |
|
are O |
|
moderate O |
|
compared O |
|
with O |
|
those O |
|
of O |
|
known O |
|
cathepsin O |
|
B O |
|
inhibitors O |
|
, O |
|
such O |
|
as O |
|
E-64 O |
|
, O |
|
which O |
|
are O |
|
active O |
|
at O |
|
a O |
|
nM O |
|
range O |
|
[ O |
|
23 O |
|
] O |
|
. O |
|
|
|
Non-enzymatic O |
|
pyridine O |
|
ring O |
|
formation O |
|
in O |
|
the O |
|
biosynthesis O |
|
of O |
|
the O |
|
rubrolone O |
|
tropolone O |
|
alkaloids O |
|
The O |
|
pyridine O |
|
ring O |
|
is O |
|
a O |
|
potent O |
|
pharmacophore O |
|
in O |
|
alkaloid O |
|
natural O |
|
products O |
|
. O |
|
|
|
The O |
|
former O |
|
transporter O |
|
was O |
|
reported O |
|
to O |
|
be O |
|
responsible O |
|
for O |
|
the O |
|
transport O |
|
of O |
|
ochratoxin O |
|
into O |
|
the O |
|
outside O |
|
of O |
|
the O |
|
cell O |
|
. O |
|
|
|
Of O |
|
the O |
|
18 O |
|
putative O |
|
genes O |
|
responsible O |
|
for O |
|
EPS273 O |
|
biosynthesis O |
|
, O |
|
four O |
|
genes O |
|
are O |
|
predicted O |
|
to O |
|
encode O |
|
regulatory O |
|
proteins O |
|
. O |
|
|
|
A O |
|
Terpene O |
|
Synthase O |
|
Is O |
|
Involved O |
|
in O |
|
the O |
|
Synthesis O |
|
of O |
|
the O |
|
Volatile O |
|
Organic O |
|
Compound O |
|
Sodorifen O |
|
of O |
|
Serratia O |
|
plymuthica O |
|
4Rx13 O |
|
Bacteria O |
|
release O |
|
a O |
|
plethora O |
|
of O |
|
volatile O |
|
organic O |
|
compounds O |
|
, O |
|
including O |
|
compounds O |
|
with O |
|
extraordinary O |
|
structures O |
|
. O |
|
|
|
Two O |
|
transporter O |
|
genes O |
|
pmxC O |
|
and O |
|
pmxD O |
|
are O |
|
present O |
|
in O |
|
the O |
|
middle O |
|
of O |
|
the O |
|
cluster O |
|
. O |
|
|
|
The O |
|
capreomycin O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
was O |
|
cloned O |
|
. O |
|
|
|
Streptomyces O |
|
sp. O |
|
ICC1 O |
|
and O |
|
Streptomyces O |
|
sp. O |
|
ICC4 O |
|
have O |
|
a O |
|
total O |
|
of O |
|
450 O |
|
subsystems O |
|
while O |
|
S. O |
|
lavendulae O |
|
has O |
|
435 O |
|
, O |
|
indicating O |
|
all O |
|
three O |
|
strains O |
|
likely O |
|
possess O |
|
similar O |
|
specific O |
|
biological O |
|
processes O |
|
and O |
|
structural O |
|
complexes O |
|
( O |
|
Overbeek O |
|
et O |
|
al. O |
|
, O |
|
2005 O |
|
) O |
|
. O |
|
|
|
The O |
|
por20 O |
|
is O |
|
homologous O |
|
to O |
|
NRPS O |
|
coding O |
|
gene O |
|
orf21 O |
|
from O |
|
anthramycin O |
|
biosynthesis O |
|
responsible O |
|
for O |
|
anthranilate O |
|
building O |
|
unit O |
|
activation O |
|
. O |
|
|
|
This O |
|
is O |
|
of O |
|
particular O |
|
interest O |
|
for O |
|
necrotrophic O |
|
pathogens O |
|
, O |
|
as O |
|
fumonisins O |
|
can O |
|
induce O |
|
plant O |
|
cell O |
|
death O |
|
by O |
|
depletion O |
|
of O |
|
extracellular O |
|
ATP O |
|
[ O |
|
78 O |
|
] O |
|
. O |
|
|
|
In O |
|
total O |
|
, O |
|
222 O |
|
SNP O |
|
’s O |
|
were O |
|
located O |
|
in O |
|
the O |
|
coding O |
|
regions O |
|
anaA O |
|
, O |
|
orf O |
|
1 O |
|
, O |
|
anaB O |
|
, O |
|
anaC O |
|
, O |
|
anaD O |
|
, O |
|
anaF O |
|
and O |
|
anaG. O |
|
One O |
|
hundred O |
|
and O |
|
thirty-four O |
|
of O |
|
the O |
|
222 O |
|
SNP O |
|
’s O |
|
were O |
|
synonymous O |
|
and O |
|
88 O |
|
were O |
|
nonsynonymous O |
|
substitutions O |
|
. O |
|
|
|
The O |
|
rifamycin O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
was O |
|
cloned O |
|
from O |
|
Amycolatopsis O |
|
mediterrane O |
|
[ O |
|
445 O |
|
] O |
|
. O |
|
|
|
Orf8 O |
|
might O |
|
therefore O |
|
represent O |
|
yet O |
|
another O |
|
fragment O |
|
of O |
|
a O |
|
PST O |
|
biosynthesis O |
|
accessory O |
|
gene O |
|
that O |
|
has O |
|
been O |
|
inactivated O |
|
. O |
|
|
|
The O |
|
tomaymycin O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
was O |
|
cloned O |
|
as O |
|
26 O |
|
kb O |
|
DNA O |
|
fragment O |
|
, O |
|
and O |
|
one O |
|
transporter O |
|
gene O |
|
, O |
|
tomM O |
|
, O |
|
was O |
|
identified O |
|
within O |
|
the O |
|
cluster O |
|
[ O |
|
132 O |
|
] O |
|
( O |
|
GB O |
|
No. O |
|
FJ768957 B-bgc-accession |
|
) O |
|
. O |
|
|
|
In O |
|
addition O |
|
to O |
|
DivA O |
|
and O |
|
DivM O |
|
, O |
|
these O |
|
include O |
|
an O |
|
α-ketoglutarate-dependent O |
|
Fe(II O |
|
) O |
|
monooxygenase/β-Asp O |
|
hydroxylase O |
|
( O |
|
DivX O |
|
; O |
|
ARD09204 B-bgc-accession |
|
) O |
|
, O |
|
a O |
|
homolog O |
|
of O |
|
DurN O |
|
( O |
|
WP_071962205.1 B-bgc-accession |
|
) O |
|
shown O |
|
to O |
|
be O |
|
involved O |
|
in O |
|
lysinoalanine O |
|
formation15–17 O |
|
( O |
|
DivN O |
|
; O |
|
ARD09209 B-bgc-accession |
|
) O |
|
, O |
|
a O |
|
SAM-dependent O |
|
methyltransferase O |
|
( O |
|
DivMT O |
|
; O |
|
ARD09206 B-bgc-accession |
|
) O |
|
, O |
|
|
|
and O |
|
an O |
|
ABC-type O |
|
transporter O |
|
( O |
|
DivT O |
|
; O |
|
ARD09207 B-bgc-accession |
|
) O |
|
. O |
|
|
|
The O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
for O |
|
nystatin O |
|
was O |
|
cloned O |
|
from O |
|
S. O |
|
noursei O |
|
ATCC11455 O |
|
[ O |
|
281 O |
|
] O |
|
. O |
|
|
|
Genbank O |
|
Accession O |
|
Number O |
|
The O |
|
GenBank O |
|
accession O |
|
number O |
|
for O |
|
the O |
|
partial O |
|
salivaricin O |
|
G32 O |
|
( O |
|
sln O |
|
) O |
|
locus O |
|
from O |
|
S. O |
|
salivarius O |
|
strain O |
|
G32 O |
|
is O |
|
JN831266 B-bgc-accession |
|
. O |
|
|
|
A O |
|
further O |
|
set O |
|
of O |
|
7 O |
|
ORFs O |
|
( O |
|
nocD O |
|
– O |
|
H O |
|
and O |
|
nocL O |
|
– O |
|
M O |
|
) O |
|
appeared O |
|
to O |
|
be O |
|
connected O |
|
to O |
|
fatty O |
|
acid O |
|
processing O |
|
, O |
|
including O |
|
two O |
|
coding O |
|
sequences O |
|
of O |
|
fatty O |
|
acyl-AMP O |
|
ligases O |
|
( O |
|
FAALs O |
|
) O |
|
and O |
|
associated O |
|
acyl O |
|
carrier O |
|
proteins O |
|
( O |
|
ACPs O |
|
) O |
|
( O |
|
nocH O |
|
and O |
|
nocL O |
|
– O |
|
M O |
|
) O |
|
. O |
|
|
|
Intriguingly O |
|
these O |
|
four O |
|
enzymes O |
|
( O |
|
AcOS O |
|
, O |
|
PaFs O |
|
, O |
|
PaPs O |
|
and O |
|
AbFS O |
|
) O |
|
are O |
|
all O |
|
bifunctional O |
|
terpene O |
|
synthases O |
|
that O |
|
each O |
|
possess O |
|
two O |
|
catalytically O |
|
independent O |
|
domains O |
|
namely O |
|
PT O |
|
and O |
|
TC O |
|
, O |
|
and O |
|
can O |
|
therefore O |
|
carry O |
|
out O |
|
both O |
|
chain O |
|
elongation O |
|
and O |
|
terpene O |
|
cyclization O |
|
. O |
|
|
|
Genome O |
|
mining O |
|
reveals O |
|
the O |
|
genus O |
|
Xanthomonas O |
|
to O |
|
be O |
|
a O |
|
promising O |
|
reservoir O |
|
for O |
|
new O |
|
bioactive O |
|
non-ribosomally O |
|
synthesized O |
|
peptides O |
|
Background O |
|
Various O |
|
bacteria O |
|
can O |
|
use O |
|
non-ribosomal O |
|
peptide O |
|
synthesis O |
|
( O |
|
NRPS O |
|
) O |
|
to O |
|
produce O |
|
peptides O |
|
or O |
|
other O |
|
small O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
|
|
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|
|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
genes O |
|
due O |
|
to O |
|
their O |
|
homology O |
|
to O |
|
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|
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|
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|
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|
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|
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|
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|
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|
previously O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
results O |
|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
. O |
|
|
|
67 O |
|
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|
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|
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|
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|
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|
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|
circinalis O |
|
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|
86 O |
|
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|
formation O |
|
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|
759 O |
|
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|
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|
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|
circinalis O |
|
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|
85 O |
|
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|
sxtE O |
|
363 O |
|
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|
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|
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|
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|
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|
90 O |
|
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|
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|
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|
a O |
|
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|
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|
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|
used O |
|
. O |
|
|
|
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|
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|
and O |
|
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|
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|
of O |
|
pallidocin O |
|
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|
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|
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|
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|
was O |
|
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|
as O |
|
A. O |
|
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|
8 O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
( O |
|
GGDC O |
|
) O |
|
using O |
|
a O |
|
digital O |
|
DNA−DNA O |
|
hybridization O |
|
( O |
|
dDDH O |
|
) O |
|
analysis O |
|
tool36 O |
|
. O |
|
|
|
HRESI(+)MS O |
|
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|
of O |
|
nanangenine O |
|
F O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
2 O |
|
. O |
|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
. O |
|
|
|
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|
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|
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|
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|
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|
methyltransferase O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
( O |
|
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|
, O |
|
the O |
|
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|
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|
response O |
|
regulatorAOK24_RS06245/S. O |
|
niveiscabieiWP_063799404.1 O |
|
(61/74)Orf3361Hypothetical O |
|
proteinAOK24_RS06240/S. O |
|
niveiscabieiWP_079056694.1 O |
|
( O |
|
56/67 O |
|
) O |
|
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|
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|
modular O |
|
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|
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|
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|
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|
I O |
|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
pathway O |
|
, O |
|
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|
a O |
|
parsimonious O |
|
route O |
|
to O |
|
epoxy-janthitrem O |
|
I O |
|
( O |
|
11 O |
|
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|
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|
G O |
|
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|
and O |
|
its O |
|
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|
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|
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|
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|
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|
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|
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|
. O |
|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
it O |
|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
. O |
|
|
|
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|
MIC O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
its O |
|
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|
congener O |
|
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|
B O |
|
( O |
|
26 O |
|
) O |
|
. O |
|
|
|
CSU93 O |
|
Pe O |
|
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|
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|
- O |
|
- O |
|
FCAKEATYKAWF O |
|
25 O |
|
% O |
|
/ O |
|
34 O |
|
% O |
|
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|
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|
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|
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|
str O |
|
. O |
|
|
|
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|
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|
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|
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|
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|
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|
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|
2 O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
. O |
|
|
|
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|
functions O |
|
of O |
|
Rv0926 O |
|
and O |
|
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|
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|
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|
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|
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|
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|
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|
ecf O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
suggest O |
|
that O |
|
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|
regulatory O |
|
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|
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|
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|
species O |
|
have O |
|
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|
. O |
|
|
|
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|
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|
polypeptide O |
|
is O |
|
a O |
|
small O |
|
lipoprotein O |
|
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|
the O |
|
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|
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|
gene O |
|
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|
in O |
|
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|
ATCC O |
|
PTA-5024 O |
|
that O |
|
confers O |
|
specific O |
|
resistance O |
|
to O |
|
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|
lantibiotics.321 O |
|
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|
the O |
|
coordinated O |
|
immunity O |
|
provided O |
|
by O |
|
LanI O |
|
and O |
|
LanEFG O |
|
proteins O |
|
, O |
|
protection O |
|
against O |
|
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|
like O |
|
lantibiotics O |
|
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|
conferred O |
|
by O |
|
several O |
|
proteins O |
|
, O |
|
MlbJQYX.321 O |
|
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|
MlbQ O |
|
sequesters O |
|
NAI-107 O |
|
and O |
|
functions O |
|
analogously O |
|
to O |
|
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|
and O |
|
SpaI O |
|
, O |
|
its O |
|
structure O |
|
shows O |
|
a O |
|
novel O |
|
topology O |
|
consisting O |
|
|
|
of O |
|
four O |
|
β O |
|
strands O |
|
topped O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
minimally O |
|
a O |
|
ketosynthase O |
|
( O |
|
KS O |
|
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|
domain O |
|
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|
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|
acyltransferase O |
|
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|
AT O |
|
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|
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|
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|
nature O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
tethers O |
|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
class O |
|
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|
polyketide O |
|
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|
machineries O |
|
. O |
|
|
|
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|
results O |
|
from O |
|
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|
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|
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|
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|
botulinum O |
|
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|
or O |
|
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|
, O |
|
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|
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|
butyricum O |
|
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|
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|
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|
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|
that O |
|
germinate O |
|
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|
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|
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|
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|
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|
of O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
produce O |
|
botulinum O |
|
toxin O |
|
. O |
|
|
|
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|
positive O |
|
electrospray O |
|
ionisation O |
|
mass O |
|
spectrometry O |
|
( O |
|
HRESI(+)MS O |
|
) O |
|
analysis O |
|
of O |
|
nanangenine O |
|
A O |
|
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|
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|
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|
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|
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|
adduct O |
|
ion O |
|
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|
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|
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|
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|
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|
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|
305.1363 O |
|
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|
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|
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|
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|
molecular O |
|
formula O |
|
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|
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|
five O |
|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
streptothricin O |
|
group O |
|
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|
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|
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|
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|
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|
spectrum O |
|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
ornithine O |
|
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|
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|
OAT O |
|
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|
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|
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|
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|
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|
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|
producing O |
|
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|
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|
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|
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|
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|
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|
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|
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|
. O |
|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
assembly O |
|
line O |
|
organizations O |
|
of O |
|
JBIR-06 O |
|
and O |
|
neoantimycin O |
|
NRPS-PKSs O |
|
were O |
|
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|
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|
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|
in O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
bearing O |
|
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|
sequence O |
|
resemblance O |
|
to O |
|
the O |
|
cyclisation O |
|
( O |
|
Cy O |
|
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|
domains O |
|
of O |
|
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|
multienzymes O |
|
, O |
|
which O |
|
typically O |
|
catalyse O |
|
the O |
|
heterocyclisation O |
|
of O |
|
cysteine O |
|
and O |
|
serine/threonine O |
|
to O |
|
thiazoline O |
|
and O |
|
oxazoline O |
|
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|
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|
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|
domain O |
|
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|
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|
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|
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|
sequence O |
|
motif O |
|
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|
( O |
|
where O |
|
x O |
|
is O |
|
any O |
|
amino O |
|
acid O |
|
) O |
|
conserved O |
|
in O |
|
Cy O |
|
domains.36 O |
|
TueC O |
|
contains O |
|
an O |
|
adenylation O |
|
domain O |
|
predicted O |
|
to O |
|
be O |
|
specific O |
|
for O |
|
the O |
|
activation O |
|
of O |
|
|
|
l-cysteine O |
|
, O |
|
and O |
|
a O |
|
peptidyl O |
|
carrier O |
|
protein O |
|
( O |
|
PCP O |
|
) O |
|
domain O |
|
to O |
|
which O |
|
the O |
|
cysteinyl O |
|
residue O |
|
is O |
|
proposed O |
|
to O |
|
become O |
|
tethered.37 O |
|
The O |
|
co-location O |
|
of O |
|
a O |
|
gene O |
|
encoding O |
|
cysteine O |
|
activation O |
|
with O |
|
an O |
|
unusual O |
|
PKS O |
|
pointed O |
|
to O |
|
the O |
|
identity O |
|
of O |
|
this O |
|
cluster O |
|
as O |
|
governing O |
|
thiotetronate O |
|
biosynthesis O |
|
. O |
|
|
|
For O |
|
that O |
|
purpose O |
|
, O |
|
a O |
|
series O |
|
of O |
|
mutant O |
|
strains O |
|
affected O |
|
in O |
|
NQ O |
|
biosynthesis O |
|
putative O |
|
genes O |
|
( O |
|
Fig. O |
|
O O |
|
5 O |
|
) O |
|
was O |
|
generated O |
|
by O |
|
disruption O |
|
of O |
|
gonP8 O |
|
, O |
|
or O |
|
individual O |
|
deletion O |
|
of O |
|
gonM4 O |
|
, O |
|
gonMT O |
|
, O |
|
gonSL O |
|
, O |
|
gonS1 O |
|
or O |
|
gonS2 O |
|
|
|
The O |
|
lichenicidins O |
|
consist O |
|
of O |
|
two O |
|
single O |
|
peptides O |
|
which O |
|
gain O |
|
their O |
|
full O |
|
activity O |
|
only O |
|
in O |
|
combination O |
|
[ O |
|
30 O |
|
] O |
|
and O |
|
they O |
|
are O |
|
encoded O |
|
by O |
|
two O |
|
different O |
|
precursor O |
|
peptides O |
|
as O |
|
well O |
|
as O |
|
modified O |
|
by O |
|
two O |
|
separate O |
|
LanM O |
|
enzymes O |
|
. O |
|
|
|
Further O |
|
, O |
|
we O |
|
exploit O |
|
these O |
|
findings O |
|
to O |
|
guide O |
|
the O |
|
design O |
|
of O |
|
artificial O |
|
cytolytic O |
|
toxins O |
|
that O |
|
are O |
|
recognized O |
|
by O |
|
the O |
|
SLS O |
|
biosynthetic O |
|
enzymes O |
|
and O |
|
others O |
|
that O |
|
are O |
|
intrinsically O |
|
cytolytic O |
|
. O |
|
|
|
We O |
|
thus O |
|
consider O |
|
that O |
|
AscR O |
|
positively O |
|
regulates O |
|
the O |
|
expression O |
|
of O |
|
both O |
|
the O |
|
asc-1 O |
|
and O |
|
-2 O |
|
cluster O |
|
genes O |
|
by O |
|
binding O |
|
to O |
|
this O |
|
motif O |
|
. O |
|
|
|
Furthermore O |
|
, O |
|
in O |
|
contrast O |
|
to O |
|
diacetylated O |
|
cylindrofridin O |
|
C O |
|
( O |
|
30 O |
|
) O |
|
, O |
|
monoacetylated O |
|
congeners O |
|
A O |
|
( O |
|
28 O |
|
) O |
|
and O |
|
B O |
|
( O |
|
29 O |
|
) O |
|
were O |
|
also O |
|
active O |
|
against O |
|
MRSA O |
|
strains O |
|
N315 O |
|
and O |
|
Mu50 O |
|
( O |
|
MICs O |
|
between O |
|
6.0 O |
|
and O |
|
21.6 O |
|
µM O |
|
) O |
|
. O |
|
|
|
In O |
|
all O |
|
cases O |
|
we O |
|
did O |
|
not O |
|
observe O |
|
growth O |
|
inhibitory O |
|
activity O |
|
in O |
|
the O |
|
concentration O |
|
range O |
|
up O |
|
to O |
|
100 O |
|
μg/ml O |
|
. O |
|
|
|
The O |
|
wzx O |
|
, O |
|
wzy O |
|
and O |
|
wzz O |
|
OPS O |
|
processing O |
|
genes O |
|
are O |
|
present O |
|
in O |
|
all O |
|
gene O |
|
clusters O |
|
, O |
|
indicating O |
|
that O |
|
all O |
|
Y. O |
|
pseudotuberculosis O |
|
serotypes O |
|
use O |
|
the O |
|
Wzx/Wzy-dependent O |
|
pathway O |
|
for O |
|
O-antigen O |
|
biosynthesis O |
|
. O |
|
|
|
Characterization O |
|
of O |
|
the O |
|
asc-2 O |
|
Cluster O |
|
Genes O |
|
. O |
|
|
|
In O |
|
this O |
|
paper O |
|
, O |
|
we O |
|
first O |
|
report O |
|
on O |
|
the O |
|
30 O |
|
kb O |
|
gene O |
|
cluster O |
|
( O |
|
23 O |
|
genes O |
|
, O |
|
acmA O |
|
to O |
|
acmW O |
|
) O |
|
involved O |
|
in O |
|
the O |
|
biosynthesis O |
|
of O |
|
these O |
|
two O |
|
antibiotics O |
|
and O |
|
a O |
|
biosynthetic O |
|
assembly O |
|
line O |
|
was O |
|
proposed O |
|
. O |
|
|
|
Results O |
|
and O |
|
discussion O |
|
Identification O |
|
of O |
|
the O |
|
talopeptin O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
To O |
|
explore O |
|
the O |
|
genetic O |
|
basis O |
|
for O |
|
the O |
|
assembly O |
|
of O |
|
1 O |
|
and O |
|
2 O |
|
we O |
|
sequenced O |
|
the O |
|
genome O |
|
of O |
|
Streptomyces O |
|
mozunensis O |
|
MK-23 O |
|
, O |
|
the O |
|
original O |
|
talopeptin O |
|
producer O |
|
. O |
|
|
|
This O |
|
analysis O |
|
predicted O |
|
that O |
|
the O |
|
operon O |
|
encodes O |
|
a O |
|
three O |
|
protein O |
|
hybrid O |
|
NRPS-PKS O |
|
assembly O |
|
line O |
|
( O |
|
alb4 O |
|
, O |
|
alb5 O |
|
and O |
|
alb6 O |
|
) O |
|
, O |
|
associated O |
|
tailoring O |
|
enzymes O |
|
( O |
|
alb2 O |
|
and O |
|
alb3 O |
|
) O |
|
and O |
|
an O |
|
export O |
|
and/or O |
|
resistance O |
|
protein O |
|
( O |
|
alb1 O |
|
) O |
|
. O |
|
|
|
In O |
|
addition O |
|
, O |
|
GliT O |
|
, O |
|
a O |
|
gliotoxin O |
|
reductase O |
|
, O |
|
plays O |
|
an O |
|
important O |
|
role O |
|
in O |
|
the O |
|
self-resistance O |
|
[ O |
|
344,345 O |
|
] O |
|
. O |
|
|
|
The O |
|
genes O |
|
for O |
|
apoprotein O |
|
( O |
|
kedA O |
|
) O |
|
and O |
|
two O |
|
transporters O |
|
( O |
|
kedX2 O |
|
and O |
|
kedX O |
|
) O |
|
are O |
|
present O |
|
within O |
|
the O |
|
cluster O |
|
. O |
|
|
|
At O |
|
first O |
|
the O |
|
leader O |
|
peptide O |
|
of O |
|
bacteriocin O |
|
KM432Bz O |
|
was O |
|
identified O |
|
from O |
|
translation O |
|
analysis O |
|
of O |
|
the O |
|
gene O |
|
cluster O |
|
sequence O |
|
and O |
|
showed O |
|
to O |
|
have O |
|
an O |
|
identical O |
|
amino O |
|
acid O |
|
sequence O |
|
to O |
|
that O |
|
shared O |
|
by O |
|
leucocin O |
|
B-Ta11a O |
|
and O |
|
leucocin O |
|
A-QU15 O |
|
( O |
|
Fig. O |
|
4 O |
|
) O |
|
, O |
|
the O |
|
latter O |
|
having O |
|
also O |
|
been O |
|
isolated O |
|
from O |
|
a O |
|
Leuc O |
|
. O |
|
|
|
oryzae O |
|
strains O |
|
X8 O |
|
- O |
|
1A O |
|
and O |
|
X11 O |
|
- O |
|
5A O |
|
, O |
|
possess O |
|
novel O |
|
NRPS O |
|
gene O |
|
clusters O |
|
and O |
|
share O |
|
related O |
|
NRPS-associated O |
|
genes O |
|
such O |
|
as O |
|
those O |
|
required O |
|
for O |
|
the O |
|
biosynthesis O |
|
of O |
|
non-proteinogenic O |
|
amino O |
|
acids O |
|
or O |
|
the O |
|
secretion O |
|
of O |
|
peptides O |
|
. O |
|
|
|
AcmX O |
|
and O |
|
AcmY O |
|
were O |
|
shown O |
|
to O |
|
share O |
|
high O |
|
homology O |
|
to O |
|
all O |
|
known O |
|
FAD-dependent O |
|
chlorinases O |
|
, O |
|
such O |
|
as O |
|
ChlB4 O |
|
( O |
|
accession O |
|
number O |
|
AAZ77674 B-bgc-accession |
|
) O |
|
from O |
|
Streptomyces O |
|
antibiotics O |
|
which O |
|
participate O |
|
in O |
|
chlorothricin O |
|
biosynthesis O |
|
( O |
|
65 O |
|
% O |
|
and O |
|
57 O |
|
% O |
|
protein O |
|
sequence O |
|
identity O |
|
respectively O |
|
) O |
|
[ O |
|
32 O |
|
] O |
|
. O |
|
|
|
Methymycin O |
|
is O |
|
a O |
|
12-membered O |
|
macrolide O |
|
that O |
|
is O |
|
isolated O |
|
from O |
|
Streptomyces O |
|
venezuelae O |
|
. O |
|
|
|
The O |
|
cluster O |
|
was O |
|
intermediated O |
|
by O |
|
an O |
|
unrelated O |
|
gene O |
|
annotated O |
|
as O |
|
hypothetical O |
|
protein O |
|
, O |
|
the O |
|
trans-isoprenyl O |
|
diphosphate O |
|
synthase O |
|
( O |
|
II5_05400 O |
|
) O |
|
. O |
|
|
|
In O |
|
addition O |
|
, O |
|
identification O |
|
of O |
|
amphipathic O |
|
α-helices O |
|
in O |
|
the O |
|
primary O |
|
sequence O |
|
and O |
|
immuno-detection O |
|
of O |
|
NisB O |
|
in O |
|
vesicles O |
|
of O |
|
L. O |
|
lactis O |
|
lead O |
|
to O |
|
the O |
|
expectation O |
|
that O |
|
NisB O |
|
may O |
|
be O |
|
membrane O |
|
associated,182 O |
|
which O |
|
also O |
|
stalled O |
|
biochemical O |
|
efforts O |
|
. O |
|
|
|
Amino O |
|
acid O |
|
sequence O |
|
of O |
|
leucocin O |
|
B-KM432Bz O |
|
precursor O |
|
( O |
|
this O |
|
study O |
|
) O |
|
was O |
|
aligned O |
|
class O |
|
IIa O |
|
bacteriocin O |
|
precursors O |
|
from O |
|
Leuconostoc O |
|
: O |
|
leucocin O |
|
A-UAL187 O |
|
, O |
|
leucocin O |
|
A-QU15 O |
|
, O |
|
leucocin O |
|
B-Ta11a O |
|
, O |
|
mesentericin O |
|
Y105 O |
|
and O |
|
pediocin O |
|
PA-1 O |
|
from O |
|
Ped O |
|
. O |
|
|
|
Based O |
|
on O |
|
these O |
|
facts O |
|
, O |
|
we O |
|
hypothesized O |
|
that O |
|
the O |
|
six-gene-mediated O |
|
reaction O |
|
is O |
|
likely O |
|
to O |
|
be O |
|
a O |
|
common O |
|
pathway O |
|
in O |
|
the O |
|
early O |
|
stage O |
|
biosynthesis O |
|
of O |
|
all O |
|
fusidane-type O |
|
antibiotics O |
|
to O |
|
give O |
|
the O |
|
key O |
|
intermediate O |
|
2 O |
|
, O |
|
which O |
|
is O |
|
then O |
|
bifurcated O |
|
to O |
|
generate O |
|
different O |
|
fusidane-type O |
|
antibiotics O |
|
under O |
|
the O |
|
action O |
|
of O |
|
different O |
|
post-modification O |
|
enzymes O |
|
( O |
|
Fig. O |
|
2D O |
|
) O |
|
. O |
|
|
|
We O |
|
also O |
|
demonstrated O |
|
that O |
|
MinCN O |
|
( O |
|
the O |
|
N-terminal O |
|
phosphatase O |
|
domain O |
|
of O |
|
MinC O |
|
) O |
|
, O |
|
MinD O |
|
( O |
|
uracil O |
|
phosphoribosyltransferase O |
|
) O |
|
, O |
|
and O |
|
MinT O |
|
( O |
|
transporter O |
|
) O |
|
function O |
|
together O |
|
as O |
|
the O |
|
safeguard O |
|
enzymes O |
|
, O |
|
which O |
|
collaboratively O |
|
constitute O |
|
an O |
|
unusual O |
|
self-resistance O |
|
system O |
|
. O |
|
|
|
Physical O |
|
map O |
|
of O |
|
the O |
|
genomic O |
|
region O |
|
containing O |
|
the O |
|
XaPPTase O |
|
gene O |
|
in O |
|
Xanthomonas O |
|
oryzae O |
|
strains O |
|
and O |
|
of O |
|
the O |
|
corresponding O |
|
region O |
|
in O |
|
other O |
|
sequenced O |
|
species O |
|
of O |
|
Xanthomonas O |
|
. O |
|
|
|
hydrophila O |
|
ATCC O |
|
7966 O |
|
99 O |
|
YP_857384 B-bgc-accession |
|
ORF3 O |
|
3295 O |
|
.. O |
|
4308 O |
|
nucleotide O |
|
sugar O |
|
epimerase O |
|
wcaG O |
|
Aeromonas O |
|
hydrophila O |
|
subsp O |
|
. O |
|
|
|
Deduced O |
|
Functions O |
|
of O |
|
Open O |
|
Reading O |
|
Frames O |
|
in O |
|
the O |
|
Tautomycetin O |
|
Biosynthetic O |
|
Gene O |
|
Cluster O |
|
gene O |
|
sizea O |
|
proposed O |
|
function O |
|
homologueb O |
|
identity%/ O |
|
similarity% O |
|
orf(−1 O |
|
) O |
|
262 O |
|
transposase O |
|
MUL_2441 O |
|
( O |
|
YP_906264 O |
|
) O |
|
32/42 O |
|
Upstream O |
|
boundary O |
|
of O |
|
the O |
|
ttn O |
|
cluster O |
|
ttnQ O |
|
472 O |
|
transcriptional O |
|
activator O |
|
StaR O |
|
( O |
|
BAC55205 O |
|
) O |
|
13/19 O |
|
ttnJ O |
|
560 O |
|
multidrug O |
|
transporter O |
|
RHA1_ro04399 O |
|
( O |
|
YP_704343 O |
|
) O |
|
49/53 O |
|
ttnI O |
|
|
|
449 O |
|
cytochrome O |
|
P450 O |
|
EryF O |
|
( O |
|
1Z8Q_A O |
|
) O |
|
30/43 O |
|
ttnR O |
|
470 O |
|
dehydratase O |
|
PrpD O |
|
( O |
|
2HP3_A O |
|
) O |
|
24/38 O |
|
ttnS O |
|
272 O |
|
unknown O |
|
PFL_4035 O |
|
( O |
|
YP_261132 O |
|
) O |
|
27/39 O |
|
ttnH O |
|
259 O |
|
thioesterase O |
|
PikAV O |
|
( O |
|
AAC69333 O |
|
) O |
|
42/53 O |
|
ttnG O |
|
926 O |
|
regulatory O |
|
protein O |
|
ThcG O |
|
( O |
|
AAD28307 O |
|
) O |
|
33/46 O |
|
ttnF O |
|
505 O |
|
l-carnitine O |
|
dehydratase O |
|
|
|
CaiB O |
|
( O |
|
1XK7_B O |
|
) O |
|
12/24 O |
|
ttnE O |
|
444 O |
|
crotonyl-CoA O |
|
reductase O |
|
Ccr O |
|
( O |
|
AAA92890 O |
|
) O |
|
75/84 O |
|
ttnD O |
|
485 O |
|
UbiD O |
|
family O |
|
decarboxylases O |
|
UbiD O |
|
( O |
|
2IDB_A O |
|
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|
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|
ttnC O |
|
209 O |
|
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|
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|
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|
( O |
|
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|
) O |
|
57/71 O |
|
ttnB O |
|
7576 O |
|
PKS O |
|
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|
6–9 O |
|
ttnA O |
|
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|
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|
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|
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|
and O |
|
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|
1–5 O |
|
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|
465 O |
|
|
|
esterase O |
|
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|
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|
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|
29/44 O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
24/37 O |
|
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|
363 O |
|
unknown O |
|
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|
( O |
|
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|
) O |
|
37/52 O |
|
ttnM O |
|
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|
hydroxylase O |
|
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|
( O |
|
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|
) O |
|
29/42 O |
|
ttnL O |
|
185 O |
|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
monooxygenase O |
|
94 O |
|
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|
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|
1,452 O |
|
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|
transporter O |
|
83 O |
|
adrD O |
|
|
|
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|
2,495 O |
|
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|
synthase O |
|
83 O |
|
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|
Proq04g062850 O |
|
336 O |
|
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|
89 O |
|
adrF O |
|
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|
256 O |
|
Short O |
|
chain O |
|
dehydrogenase O |
|
91 O |
|
adrG O |
|
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|
316 O |
|
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|
87 O |
|
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|
Proq04g062880a O |
|
476 O |
|
FAD-dependent O |
|
monooxygenase O |
|
83 O |
|
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|
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|
245 O |
|
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|
cyclase O |
|
94 O |
|
|
|
adrJ O |
|
Proq04g062900 O |
|
496 O |
|
Acetyltransferase O |
|
85 O |
|
adrK O |
|
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|
278 O |
|
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|
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|
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|
several O |
|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
|
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|
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|
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|
and O |
|
stereochemistry O |
|
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|
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|
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|
yet O |
|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
were O |
|
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|
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|
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|
tenebrarius O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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also O |
|
reported O |
|
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|
display O |
|
cytotoxicity O |
|
against O |
|
human O |
|
lung O |
|
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|
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|
, O |
|
colon O |
|
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|
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|
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|
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|
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|
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|
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|
liver O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
|
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|
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|
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|
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|
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|
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|
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graminearum O |
|
. O |
|
|
|
Gene O |
|
acmE O |
|
located O |
|
between O |
|
acmD O |
|
and O |
|
acmF O |
|
whose O |
|
translated O |
|
product O |
|
weakly O |
|
resemble O |
|
an O |
|
aminopeptidase O |
|
from O |
|
Xanthomonas O |
|
campestris O |
|
( O |
|
accession O |
|
number O |
|
BAA11623 B-bgc-accession |
|
, O |
|
20 O |
|
% O |
|
identity O |
|
) O |
|
which O |
|
have O |
|
been O |
|
demonstrated O |
|
in O |
|
vitro O |
|
to O |
|
catalyse O |
|
a O |
|
hydrolysis O |
|
reaction O |
|
of O |
|
ascamycin O |
|
to O |
|
dealanylascamycin O |
|
causing O |
|
the O |
|
host O |
|
to O |
|
become O |
|
susceptible O |
|
to O |
|
ascamycin O |
|
[ O |
|
36 O |
|
] O |
|
. O |
|
|
|
Also O |
|
, O |
|
the O |
|
type O |
|
F7 O |
|
toxin O |
|
gene O |
|
cluster O |
|
lacked O |
|
a O |
|
botR O |
|
regulatory O |
|
gene O |
|
, O |
|
as O |
|
is O |
|
the O |
|
case O |
|
with O |
|
the O |
|
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|
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|
botulinum O |
|
type O |
|
E O |
|
, O |
|
nonproteolytic O |
|
C. O |
|
butyricum O |
|
type O |
|
E O |
|
and O |
|
nonproteolytic O |
|
C. O |
|
botulinum O |
|
type O |
|
F6 O |
|
toxin O |
|
gene O |
|
clusters O |
|
[ O |
|
8 O |
|
] O |
|
, O |
|
[ O |
|
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|
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|
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|
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|
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|
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|
. O |
|
|
|
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|
investigated O |
|
the O |
|
occurrence O |
|
of O |
|
type O |
|
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|
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|
genes O |
|
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|
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|
. O |
|
|
|
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|
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|
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|
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|
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|
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|
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genes O |
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|
|
|
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|
Function O |
|
A-500359 O |
|
A-503083 O |
|
A-102395 O |
|
Fe(II)- O |
|
and O |
|
αKG-dependent O |
|
dioxygenase O |
|
orf7 O |
|
capD O |
|
cpr18 O |
|
Capuramycin-2′-O-carbamoyltransferase O |
|
orf8 O |
|
capB O |
|
NA O |
|
Putative O |
|
3-ketoreductase O |
|
orf9 O |
|
capC O |
|
cpr20 O |
|
Fe(II)-dependent O |
|
, O |
|
αKG O |
|
: O |
|
UMP O |
|
dioxygenase O |
|
orf10 O |
|
capA O |
|
cpr19 O |
|
Putative O |
|
2,3-dehydratase O |
|
|
|
orf11 O |
|
capE O |
|
cpr21 O |
|
Putative O |
|
4-epimerase O |
|
orf12 O |
|
capF O |
|
cpr22 O |
|
PLP-dependent O |
|
monooxygenase-decarboxylase O |
|
orf12 O |
|
’ O |
|
cap15 O |
|
cpr23 O |
|
Putative O |
|
glycosyl O |
|
transferase O |
|
orf13 O |
|
capG O |
|
cpr24 O |
|
l-Thr O |
|
: O |
|
uridine-5′-aldehyde O |
|
transaldolase O |
|
orf14 O |
|
capH O |
|
cpr25 O |
|
Putative O |
|
pyrophosphatase O |
|
orf15 O |
|
capI O |
|
cpr26 O |
|
Putative O |
|
CO O |
|
dehydrogenase O |
|
orf16 O |
|
capJ O |
|
|
|
cpr28 O |
|
Putative O |
|
O-methyltransferase O |
|
orf16 O |
|
’ O |
|
capK O |
|
cpr29 O |
|
Putative O |
|
CO O |
|
dehydrogenase O |
|
orf17 O |
|
capL O |
|
cpr30 O |
|
Putative O |
|
CO O |
|
dehydrogenase O |
|
orf18 O |
|
capM O |
|
cpr31 O |
|
Putative O |
|
ABC O |
|
transporter O |
|
orf19 O |
|
capN O |
|
NA O |
|
Putative O |
|
ABC O |
|
transporter O |
|
orf20 O |
|
capO O |
|
NA O |
|
Capuramycin O |
|
3′′-phosphotransferase O |
|
orf21 O |
|
capP O |
|
cpr17 O |
|
UDP-glucose-4,6-dehydratase O |
|
orf22 O |
|
|
|
capQ O |
|
NA O |
|
Glucose-1-phosphate O |
|
thymidylyltransferase O |
|
orf23 O |
|
capR O |
|
NA O |
|
Putative O |
|
carboxyl O |
|
methyltransferase O |
|
orf24 O |
|
capS O |
|
cpr27 O |
|
Putative O |
|
l-ACL O |
|
C-methyltransferase O |
|
orf25 O |
|
capT O |
|
NA O |
|
Nonribosomal O |
|
peptide O |
|
synthetase O |
|
orf26 O |
|
capU O |
|
NA O |
|
Nonribosomal O |
|
peptide O |
|
synthetase O |
|
orf27 O |
|
capV O |
|
NA O |
|
Transacylase O |
|
orf28 O |
|
capW O |
|
cpr51 O |
|
Antimycobacterial O |
|
activities O |
|
of O |
|
several O |
|
capuramycin O |
|
analogs O |
|
prepared O |
|
through O |
|
|
|
semisynthesis O |
|
. O |
|
|
|
Our O |
|
findings O |
|
suggest O |
|
that O |
|
Pse O |
|
biosynthesis O |
|
in O |
|
T. O |
|
forsythia O |
|
ATCC O |
|
43037 O |
|
follows O |
|
essentially O |
|
the O |
|
same O |
|
biosynthetic O |
|
route O |
|
as O |
|
in O |
|
C. O |
|
jejuni O |
|
and O |
|
H. O |
|
pylori O |
|
( O |
|
Schoenhofen O |
|
et O |
|
al. O |
|
2006b O |
|
) O |
|
. O |
|
|
|
To O |
|
increase O |
|
sensitivity O |
|
, O |
|
we O |
|
adopted O |
|
a O |
|
liquid O |
|
phase O |
|
hemolysis O |
|
assay O |
|
. O |
|
|
|
Besides O |
|
its O |
|
inhibitory O |
|
effect O |
|
against O |
|
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|
cell O |
|
growth O |
|
, O |
|
the O |
|
anti-metastatic O |
|
activity O |
|
of O |
|
compound O |
|
4 O |
|
against O |
|
AGS O |
|
gastric O |
|
cancer O |
|
cell O |
|
line O |
|
was O |
|
also O |
|
determined O |
|
through O |
|
migration O |
|
and O |
|
invasion O |
|
assays O |
|
. O |
|
|
|
Regulation O |
|
of O |
|
antimycin O |
|
biosynthesis O |
|
by O |
|
the O |
|
orphan O |
|
ECF O |
|
RNA O |
|
polymerase O |
|
sigma O |
|
factor O |
|
σAntA O |
|
Antimycins O |
|
are O |
|
an O |
|
extended O |
|
family O |
|
of O |
|
depsipeptides O |
|
that O |
|
are O |
|
made O |
|
by O |
|
filamentous O |
|
actinomycete O |
|
bacteria O |
|
and O |
|
were O |
|
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|
isolated O |
|
more O |
|
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|
60 O |
|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
of O |
|
coding O |
|
sequence O |
|
, O |
|
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|
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|
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|
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|
E. O |
|
glyceriae O |
|
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|
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|
which O |
|
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|
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|
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|
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|
coding O |
|
sequence O |
|
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|
|
|
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|
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|
a O |
|
medium-sized O |
|
spirotetronate O |
|
class O |
|
antibiotic O |
|
, O |
|
and O |
|
inhibits O |
|
pyruvate O |
|
carboxylases O |
|
from O |
|
rat O |
|
liver O |
|
and O |
|
Azotobacter O |
|
vinelandii O |
|
and O |
|
cholesterol O |
|
biosynthesis O |
|
. O |
|
|
|
LangelandFirmicutes O |
|
CLI_0567 O |
|
clostridiolysin O |
|
S O |
|
Thermoanaerobacter O |
|
mathranii O |
|
mathranii O |
|
A3 O |
|
, O |
|
DSM O |
|
11426Firmicutes O |
|
Tmath_0475 O |
|
* O |
|
* O |
|
|
|
M. O |
|
smegmatis O |
|
M. O |
|
abscessus O |
|
M. O |
|
chelonae O |
|
Gene O |
|
Gene O |
|
n O |
|
° O |
|
Proposed O |
|
function(a O |
|
) O |
|
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|
n O |
|
° O |
|
% O |
|
( O |
|
b O |
|
) O |
|
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|
n O |
|
° O |
|
% O |
|
( O |
|
b O |
|
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|
O O |
|
mmpS4 O |
|
MSMEG0373 O |
|
Membrane O |
|
associated O |
|
|
|
The O |
|
polymyxin O |
|
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|
gene O |
|
cluster O |
|
was O |
|
cloned O |
|
from O |
|
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|
polymyxa O |
|
and O |
|
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|
[ O |
|
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|
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|
. O |
|
|
|
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|
( O |
|
astromicin O |
|
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|
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|
an O |
|
aminoglycoside O |
|
antibiotic O |
|
that O |
|
is O |
|
produced O |
|
by O |
|
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|
olivasterospora O |
|
, O |
|
and O |
|
fmrO O |
|
encoding O |
|
16S O |
|
rRNA O |
|
methyltransferase O |
|
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|
plays O |
|
a O |
|
role O |
|
in O |
|
self-resistance O |
|
[ O |
|
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|
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|
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|
|
|
Results O |
|
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|
of O |
|
a O |
|
cosmid O |
|
library O |
|
of O |
|
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|
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|
genomic O |
|
DNA O |
|
As O |
|
screening O |
|
probes O |
|
, O |
|
the O |
|
DNA O |
|
fragments O |
|
of O |
|
KS O |
|
, O |
|
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|
and O |
|
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|
protein O |
|
were O |
|
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|
amplified O |
|
from O |
|
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|
griseus O |
|
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|
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|
chromosomal O |
|
DNA O |
|
. O |
|
|
|
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|
] O |
|
Sequence O |
|
ID O |
|
: O |
|
ref|YP_001569863.1| O |
|
67/81 O |
|
11 O |
|
wbuC O |
|
12380:12877 O |
|
165 O |
|
unknown O |
|
conserved O |
|
LPS O |
|
biosynthetic O |
|
protein O |
|
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|
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|
enterica O |
|
subsp O |
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. O |
|
|
|
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species O |
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|
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pseudotuberculosis/Y. O |
|
pestis O |
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|
similis O |
|
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|
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|
et O |
|
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|
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|
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|
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|
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|
the O |
|
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|
characterised O |
|
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|
wautersii O |
|
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|
previously O |
|
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|
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|
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group O |
|
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|
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|
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to O |
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potential O |
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|
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|
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|
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|
|
|
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development O |
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|
|
|
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|
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identity O |
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the O |
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|
aflatoxin O |
|
pathway O |
|
transcriptional O |
|
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|
|
|
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|
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|
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|
specificity O |
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
genera O |
|
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|
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|
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|
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|
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|
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|
identified O |
|
as O |
|
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|
phenazine O |
|
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|
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|
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|
|
|
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|
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|
region O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
gene O |
|
cluster O |
|
from O |
|
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|
ambigua O |
|
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|
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|
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|
7 O |
|
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|
. O |
|
|
|
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|
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|
sp. O |
|
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|
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|
srcmRII O |
|
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|
family O |
|
transcriptional O |
|
regulator186CmmRII O |
|
[ O |
|
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|
griseus O |
|
subsp O |
|
. O |
|
|
|
inebrians O |
|
E818 O |
|
was O |
|
arranged O |
|
similarly O |
|
to O |
|
that O |
|
of O |
|
P. O |
|
ipomoeae O |
|
and O |
|
the O |
|
Claviceps O |
|
species O |
|
, O |
|
it O |
|
was O |
|
broken O |
|
into O |
|
two O |
|
clusters O |
|
, O |
|
one O |
|
of O |
|
which O |
|
ended O |
|
in O |
|
a O |
|
telomere O |
|
located O |
|
one O |
|
bp O |
|
from O |
|
the O |
|
cloA O |
|
stop O |
|
codon O |
|
. O |
|
|
|
Cultures O |
|
of O |
|
all O |
|
eight O |
|
available O |
|
isolates O |
|
of O |
|
six O |
|
Metarhizium O |
|
species O |
|
, O |
|
but O |
|
not O |
|
of O |
|
M. O |
|
album O |
|
, O |
|
produced O |
|
detectable O |
|
levels O |
|
of O |
|
swainsonine O |
|
( O |
|
Table O |
|
S1 O |
|
in O |
|
File O |
|
S1 O |
|
) O |
|
, O |
|
showing O |
|
a O |
|
strong O |
|
correlation O |
|
of O |
|
SWN O |
|
cluster O |
|
presence O |
|
and O |
|
swainsonine O |
|
production O |
|
. O |
|
|
|
– O |
|
– O |
|
II O |
|
– O |
|
– O |
|
– O |
|
– O |
|
idtJ O |
|
|
|
Another O |
|
ORF O |
|
( O |
|
nocP O |
|
) O |
|
was O |
|
annotated O |
|
as O |
|
a O |
|
simple O |
|
PKS O |
|
gene O |
|
. O |
|
|
|
If O |
|
the O |
|
proposed O |
|
pathway O |
|
( O |
|
intramolecular O |
|
hydroalkoxylation O |
|
at O |
|
C-8 O |
|
) O |
|
proceeds O |
|
enzymatically O |
|
( O |
|
catalyzed O |
|
by O |
|
MarG O |
|
) O |
|
, O |
|
then O |
|
the O |
|
premarineosin O |
|
A O |
|
( O |
|
9 O |
|
) O |
|
might O |
|
be O |
|
the O |
|
intermediate O |
|
of O |
|
marineosins O |
|
A O |
|
and O |
|
B. O |
|
It O |
|
is O |
|
noteworthy O |
|
that O |
|
the O |
|
premarineosin O |
|
B O |
|
( O |
|
11 O |
|
) O |
|
most O |
|
likely O |
|
arises O |
|
from O |
|
an O |
|
inversion O |
|
of O |
|
the O |
|
aminal O |
|
nitrogen O |
|
of O |
|
premarineosin O |
|
A O |
|
( O |
|
9 O |
|
) O |
|
under O |
|
pathway O |
|
conditions O |
|
where O |
|
the O |
|
two O |
|
isomers O |
|
differ O |
|
only O |
|
in O |
|
stereochemistry O |
|
at O |
|
the O |
|
spiro O |
|
aminal O |
|
carbon O |
|
( O |
|
C-8 O |
|
) O |
|
. O |
|
|
|
These O |
|
results O |
|
confirm O |
|
that O |
|
TalE O |
|
catalyzes O |
|
the O |
|
second O |
|
step O |
|
in O |
|
the O |
|
biosynthesis O |
|
of O |
|
1 O |
|
and O |
|
2 O |
|
using O |
|
the O |
|
TalD O |
|
product O |
|
4 O |
|
and O |
|
ATP O |
|
as O |
|
substrates O |
|
to O |
|
form O |
|
5 O |
|
. O |
|
|
|
A O |
|
likely O |
|
product O |
|
from O |
|
cluster O |
|
5 O |
|
was O |
|
predicted O |
|
as O |
|
ectoine O |
|
, O |
|
its O |
|
BGC O |
|
has O |
|
high O |
|
similarity O |
|
with O |
|
its O |
|
counterpart O |
|
in O |
|
Streptomyces O |
|
anulatus O |
|
. O |
|
|
|
Polyketides O |
|
are O |
|
biosynthesized O |
|
via O |
|
the O |
|
sequential O |
|
condensations O |
|
of O |
|
small O |
|
carboxylic O |
|
acid O |
|
subunits O |
|
with O |
|
an O |
|
acyl O |
|
starter O |
|
in O |
|
a O |
|
fashion O |
|
that O |
|
is O |
|
reminiscent O |
|
of O |
|
fatty O |
|
acid O |
|
biosynthesis O |
|
. O |
|
|
|
Among O |
|
them O |
|
, O |
|
six O |
|
genes O |
|
, O |
|
fusA O |
|
, O |
|
fusB2 O |
|
, O |
|
fusB3 O |
|
, O |
|
fusB4 O |
|
, O |
|
fusC2 O |
|
and O |
|
fusD O |
|
encode O |
|
proteins O |
|
with O |
|
high O |
|
sequence O |
|
similarity O |
|
( O |
|
37%-65 O |
|
% O |
|
identity O |
|
) O |
|
to O |
|
those O |
|
encoded O |
|
by O |
|
helA O |
|
, O |
|
helB2 O |
|
, O |
|
helB4 O |
|
, O |
|
helB1 O |
|
, O |
|
helC O |
|
and O |
|
helD2 O |
|
in O |
|
the O |
|
gene O |
|
cluster O |
|
of O |
|
helvolic O |
|
acid O |
|
. O |
|
|
|
Restoration O |
|
of O |
|
antifungal O |
|
production O |
|
close O |
|
to O |
|
wild O |
|
type O |
|
levels O |
|
indicates O |
|
that O |
|
control O |
|
of O |
|
filipin O |
|
production O |
|
by O |
|
phosphate O |
|
is O |
|
mediated O |
|
by O |
|
PhoRP O |
|
in O |
|
S. O |
|
filipinensis O |
|
. O |
|
|
|
In O |
|
addition O |
|
to O |
|
revealing O |
|
plausible O |
|
candidates O |
|
for O |
|
the O |
|
biosynthetic O |
|
gene O |
|
clusters O |
|
for O |
|
thiotetronates O |
|
( O |
|
1 O |
|
) O |
|
and O |
|
( O |
|
4 O |
|
) O |
|
, O |
|
a O |
|
search O |
|
of O |
|
published O |
|
genome O |
|
sequences O |
|
using O |
|
the O |
|
bioinformatics O |
|
tool O |
|
antiSMASH3 O |
|
revealed O |
|
a O |
|
gene O |
|
cluster O |
|
similar O |
|
to O |
|
that O |
|
for O |
|
TLM O |
|
in O |
|
the O |
|
fully-sequenced O |
|
genome O |
|
of O |
|
Streptomyces O |
|
cattleya O |
|
NRRL O |
|
8057 O |
|
(SCAT5757-SCAT5761).45 O |
|
Manual O |
|
BLAST O |
|
searching O |
|
uncovered O |
|
a O |
|
further O |
|
two O |
|
Tü O |
|
3010-like O |
|
gene O |
|
clusters O |
|
in O |
|
, O |
|
respectively O |
|
, O |
|
Streptomyces O |
|
afghanensis O |
|
277 O |
|
( O |
|
NCBI O |
|
|
|
identifiers O |
|
EPJ35918 B-bgc-accession |
|
to O |
|
EPJ34243 B-bgc-accession |
|
) O |
|
and O |
|
Streptomyces O |
|
incarnatus O |
|
NRRL O |
|
8089 O |
|
( O |
|
NCBI O |
|
identifiers O |
|
ABB07_06605 O |
|
to O |
|
ABB07_06685 O |
|
) O |
|
. O |
|
|
|
In O |
|
this O |
|
test O |
|
, O |
|
S. O |
|
salivarius O |
|
G32 O |
|
and O |
|
S. O |
|
dysgalactiae O |
|
61 O |
|
both O |
|
gave O |
|
P-type O |
|
436 O |
|
inhibitory O |
|
profiles O |
|
identical O |
|
to O |
|
that O |
|
of O |
|
S. O |
|
pyogenes O |
|
FF22 O |
|
( O |
|
Table O |
|
1 O |
|
) O |
|
. O |
|
|
|
hydrophila O |
|
ATCC O |
|
7966 O |
|
100 O |
|
YP_857391 B-bgc-accession |
|
ORF10 O |
|
10651 O |
|
.. O |
|
11673 O |
|
RimK-like O |
|
protein O |
|
rimK O |
|
Aeromonas O |
|
hydrophila O |
|
subsp O |
|
. O |
|
|
|
Enediyne O |
|
Antitumor O |
|
Antibiotics O |
|
The O |
|
enediyne O |
|
antitumor O |
|
antibiotics O |
|
are O |
|
a O |
|
growing O |
|
family O |
|
of O |
|
natural O |
|
products O |
|
with O |
|
novel O |
|
molecular O |
|
architecture O |
|
with O |
|
triple O |
|
bonds O |
|
, O |
|
and O |
|
unique O |
|
biological O |
|
activity O |
|
. O |
|
|
|
A O |
|
set O |
|
of O |
|
eight O |
|
genes O |
|
, O |
|
designated O |
|
lomo1–8 O |
|
, O |
|
were O |
|
most O |
|
likely O |
|
to O |
|
code O |
|
for O |
|
enzymes O |
|
relating O |
|
to O |
|
the O |
|
shikimate O |
|
pathway O |
|
[ O |
|
2 O |
|
] O |
|
. O |
|
|
|
It O |
|
is O |
|
tempting O |
|
to O |
|
speculate O |
|
that O |
|
they O |
|
may O |
|
be O |
|
involved O |
|
in O |
|
the O |
|
formation O |
|
of O |
|
the O |
|
N-oxide O |
|
group O |
|
found O |
|
in O |
|
JBIR-46 O |
|
and O |
|
JBIR-48 O |
|
, O |
|
but O |
|
so O |
|
far O |
|
there O |
|
is O |
|
no O |
|
direct O |
|
evidence O |
|
to O |
|
support O |
|
this O |
|
speculation O |
|
. O |
|
|
|
A. O |
|
circinalis O |
|
AWQC131C O |
|
PST O |
|
biosynthesis O |
|
gene O |
|
cluster O |
|
is O |
|
available O |
|
under O |
|
accession O |
|
number O |
|
DQ787201 B-bgc-accession |
|
. O |
|
|
|
and O |
|
Aspergillus O |
|
spp O |
|
. O |
|
|
|
The O |
|
results O |
|
revealed O |
|
that O |
|
only O |
|
the O |
|
addition O |
|
of O |
|
the O |
|
ferric O |
|
iron O |
|
salt O |
|
FeCl3 O |
|
( O |
|
as O |
|
well O |
|
as O |
|
the O |
|
addition O |
|
of O |
|
ferrous O |
|
iron O |
|
FeSO4 O |
|
; O |
|
data O |
|
not O |
|
shown O |
|
) O |
|
triggered O |
|
production O |
|
of O |
|
the O |
|
green O |
|
pigmented O |
|
ferroverdin O |
|
A O |
|
by O |
|
S. O |
|
lunaelactis O |
|
MM109 O |
|
T O |
|
( O |
|
Fig. O |
|
O O |
|
2A O |
|
) O |
|
|
|
In O |
|
addition O |
|
to O |
|
structural O |
|
or O |
|
defensive O |
|
roles O |
|
during O |
|
fungal O |
|
disease O |
|
, O |
|
recent O |
|
work O |
|
in O |
|
M. O |
|
fijiensis O |
|
demonstrated O |
|
that O |
|
DHN-melanin O |
|
generates O |
|
highly O |
|
reactive O |
|
oxygen O |
|
species O |
|
that O |
|
may O |
|
facilitate O |
|
host O |
|
cell O |
|
death O |
|
[ O |
|
53 O |
|
] O |
|
. O |
|
|
|
The O |
|
biosynthetic O |
|
gene O |
|
cluster O |
|
was O |
|
cloned O |
|
from O |
|
Saccharothrix O |
|
( O |
|
Lechevalieria O |
|
) O |
|
aerocolonigenes O |
|
[ O |
|
380,381 O |
|
] O |
|
. O |
|
|
|
It O |
|
should O |
|
be O |
|
noted O |
|
that O |
|
AviCys O |
|
residues O |
|
are O |
|
also O |
|
observed O |
|
in O |
|
two O |
|
other O |
|
classes O |
|
of O |
|
RiPP O |
|
natural O |
|
products O |
|
, O |
|
namely O |
|
linaridins297,298 O |
|
and O |
|
thioviridamides.299 O |
|
Although O |
|
linaridins O |
|
such O |
|
as O |
|
cypemycin297 O |
|
and O |
|
grisemycin298 O |
|
contain O |
|
the O |
|
dehydro O |
|
amino O |
|
acid O |
|
Dhb O |
|
, O |
|
the O |
|
biosynthetic O |
|
gene O |
|
clusters O |
|
for O |
|
these O |
|
molecules O |
|
do O |
|
not O |
|
encode O |
|
obvious O |
|
homologues O |
|
of O |
|
either O |
|
the O |
|
lanthipeptide O |
|
dehydratase O |
|
that O |
|
is O |
|
necessary O |
|
for O |
|
installation O |
|
of O |
|
the O |
|
Dha/Dhb O |
|
or O |
|
the O |
|
lanthipeptide O |
|
|
|
cyclase O |
|
implicated O |
|
in O |
|
AviCys O |
|
formation O |
|
. O |
|
|
|
jejuni O |
|
legI O |
|
(Cj1327)56391Legionaminic O |
|
acid O |
|
synthaseSchoenhofen O |
|
et O |
|
al. O |
|
(2009)BFO_1063C O |
|
. O |
|
|
|
These O |
|
results O |
|
confirm O |
|
that O |
|
non-identical O |
|
parts O |
|
of O |
|
the O |
|
puwainaphycin O |
|
variants O |
|
are O |
|
situated O |
|
in O |
|
the O |
|
unusual O |
|
FA O |
|
aliphatic O |
|
chain O |
|
whereas O |
|
the O |
|
remaining O |
|
part O |
|
of O |
|
the O |
|
molecule O |
|
is O |
|
identical O |
|
for O |
|
all O |
|
the O |
|
puwainaphycin O |
|
analogs O |
|
, O |
|
based O |
|
on O |
|
the O |
|
PUW-F/PUW-G O |
|
structures O |
|
. O |
|
|
|
The O |
|
NRPS O |
|
OhmA O |
|
encodes O |
|
12 O |
|
modules O |
|
containing O |
|
the O |
|
entire O |
|
41 O |
|
domains O |
|
. O |
|
|
|
The O |
|
lipotetradecadepsipeptides O |
|
are O |
|
assembled O |
|
by O |
|
XtlA O |
|
, O |
|
XtlB O |
|
and O |
|
XtlC O |
|
, O |
|
three O |
|
co-linearly O |
|
operating O |
|
non-ribosomal O |
|
peptide O |
|
synthetases O |
|
( O |
|
NRPSs O |
|
) O |
|
displaying O |
|
similarity O |
|
in O |
|
modular O |
|
architecture O |
|
with O |
|
the O |
|
entolysin-producing O |
|
enzymes O |
|
of O |
|
the O |
|
entomopathogenic O |
|
Pseudomonas O |
|
entomophila O |
|
L48 O |
|
. O |
|
|
|
Considering O |
|
the O |
|
puwainaphycin O |
|
F/G O |
|
variants O |
|
reported O |
|
in O |
|
this O |
|
study O |
|
, O |
|
the O |
|
A-domain O |
|
appears O |
|
to O |
|
accept O |
|
both O |
|
asparagine O |
|
and O |
|
glutamine O |
|
as O |
|
a O |
|
substrate O |
|
at O |
|
a O |
|
defined O |
|
rate O |
|
, O |
|
as O |
|
further O |
|
demonstrated O |
|
by O |
|
MS O |
|
measurements O |
|
. O |
|
|
|
Antibiotic O |
|
production O |
|
in O |
|
S. O |
|
natalensis O |
|
, O |
|
S. O |
|
lividans O |
|
and O |
|
S. O |
|
lydicus O |
|
ΔphoP O |
|
mutants O |
|
is O |
|
also O |
|
sensitive O |
|
to O |
|
high O |
|
Pi O |
|
concentrations O |
|
[ O |
|
22,33,34 O |
|
] O |
|
, O |
|
thus O |
|
it O |
|
seems O |
|
likely O |
|
that O |
|
a O |
|
yet O |
|
unidentified O |
|
PhoP-independent O |
|
mechanism O |
|
blocks O |
|
antibiotic O |
|
biosynthesis O |
|
under O |
|
excess O |
|
phosphate O |
|
conditions O |
|
. O |
|
|
|
We O |
|
believe O |
|
SMA2293-SMA2288 O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
transporters O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
aim O |
|
of O |
|
these O |
|
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|
was O |
|
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|
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|
if O |
|
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|
production O |
|
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|
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|
could O |
|
be O |
|
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|
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|
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|
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|
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|
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|
employing O |
|
genomic O |
|
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|
strain O |
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|
|
|
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|
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|
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|
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|
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|
that O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
types O |
|
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|
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|
, O |
|
K6 O |
|
, O |
|
K16 O |
|
, O |
|
K54 O |
|
, O |
|
K58 O |
|
, O |
|
K63 O |
|
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|
that O |
|
contain O |
|
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|
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|
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|
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|
unit O |
|
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|
both O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
and O |
|
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|
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|
a O |
|
nucleotide O |
|
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|
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|
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|
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|
activity O |
|
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|
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|
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|
and O |
|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
which O |
|
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|
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|
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|
effect O |
|
on O |
|
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|
inhibition O |
|
and O |
|
anti-TB O |
|
activity O |
|
. O |
|
|
|
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|
and O |
|
genetic O |
|
characterization O |
|
of O |
|
gassericin O |
|
E O |
|
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|
a O |
|
novel O |
|
co-culture O |
|
inducible O |
|
bacteriocin O |
|
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|
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|
gasseri O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
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|
report O |
|
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|
identification O |
|
of O |
|
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|
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|
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|
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|
gene O |
|
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|
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|
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|
marine O |
|
actinomycete O |
|
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|
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|
subsp O |
|
. O |
|
|
|
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|
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|
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|
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|
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|
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|
showed O |
|
the O |
|
desired O |
|
negative O |
|
sodorifen O |
|
phenotype O |
|
. O |
|
|
|
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|
mojavensis O |
|
RO-H-1 O |
|
ZP_10514325.1 B-bgc-accession |
|
BmojR_010100015748 O |
|
46 O |
|
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|
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|
12 O |
|
. O |
|
|
|
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|
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|
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|
this O |
|
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|
activity O |
|
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|
in O |
|
line O |
|
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|
other O |
|
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|
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|
products O |
|
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|
as O |
|
the O |
|
diterpene O |
|
dictyol O |
|
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|
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|
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|
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|
oroidin29 O |
|
. O |
|
|
|
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|
determine O |
|
whether O |
|
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|
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|
genes O |
|
were O |
|
responsible O |
|
for O |
|
the O |
|
biosynthesis O |
|
of O |
|
KK-1 O |
|
, O |
|
we O |
|
performed O |
|
heterologous O |
|
production O |
|
of O |
|
KK-1 O |
|
in O |
|
Aspergillus O |
|
oryzae O |
|
by O |
|
introduction O |
|
of O |
|
the O |
|
cluster O |
|
genes O |
|
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|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
gene O |
|
cluster O |
|
for O |
|
landomycin O |
|
E O |
|
was O |
|
cloned O |
|
from O |
|
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|
globisporus O |
|
[ O |
|
360 O |
|
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|
, O |
|
and O |
|
that O |
|
for O |
|
landomycin O |
|
A O |
|
was O |
|
cloned O |
|
from O |
|
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|
cyanogenus O |
|
[ O |
|
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|
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|
. O |
|
|
|
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|
adenylation O |
|
domain O |
|
sequences O |
|
of O |
|
McyB1 O |
|
and O |
|
McyC O |
|
from O |
|
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|
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|
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|
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|
have O |
|
gone O |
|
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|
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|
events O |
|
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|
their O |
|
sequences O |
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
) O |
|
. O |
|
|
|
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|
growth O |
|
inhibition O |
|
activity O |
|
in O |
|
all O |
|
cases O |
|
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|
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|
( O |
|
Figure O |
|
5 O |
|
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|
. O |
|
|
|
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|
( O |
|
fradiomycin O |
|
) O |
|
, O |
|
paromomycin O |
|
, O |
|
and O |
|
lividomycin O |
|
belong O |
|
to O |
|
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|
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|
aminoglycoside O |
|
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|
. O |
|
|
|
Bioinformatic O |
|
analysis O |
|
of O |
|
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|
substrate O |
|
specificity O |
|
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|
all O |
|
nine O |
|
adenylation O |
|
domains O |
|
indicated O |
|
that O |
|
the O |
|
sequence O |
|
of O |
|
the O |
|
NRPS O |
|
modules O |
|
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|
well O |
|
collinear O |
|
with O |
|
the O |
|
order O |
|
of O |
|
amino O |
|
acids O |
|
in O |
|
pelgipeptin O |
|
. O |
|
|
|
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|
E O |
|
is O |
|
produced O |
|
by O |
|
S. O |
|
globisporus O |
|
, O |
|
and O |
|
shows O |
|
antitumor O |
|
activity O |
|
which O |
|
is O |
|
only O |
|
mildly O |
|
affected O |
|
by O |
|
multidrug O |
|
resistance-mediated O |
|
drug O |
|
efflux O |
|
. O |
|
|
|
Sequences O |
|
of O |
|
phzE O |
|
genes O |
|
, O |
|
which O |
|
are O |
|
part O |
|
of O |
|
the O |
|
phenazine O |
|
biosynthetic O |
|
pathway O |
|
, O |
|
were O |
|
used O |
|
to O |
|
design O |
|
one O |
|
universal O |
|
primer O |
|
system O |
|
and O |
|
to O |
|
analyze O |
|
the O |
|
ability O |
|
of O |
|
bacteria O |
|
to O |
|
produce O |
|
phenazine O |
|
. O |
|
|
|
Alkaloid O |
|
biosynthesis O |
|
gene O |
|
origins O |
|
in O |
|
selected O |
|
hybrid O |
|
endophyte O |
|
strains O |
|
a. O |
|
E. O |
|
can O |
|
. O |
|
|
|
Atypical O |
|
Listeria O |
|
innocua O |
|
strains O |
|
possess O |
|
an O |
|
intact O |
|
LIPI-3 O |
|
Background O |
|
Listeria O |
|
monocytogenes O |
|
is O |
|
a O |
|
food-borne O |
|
pathogen O |
|
which O |
|
is O |
|
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|
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|
agent O |
|
of O |
|
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|
and O |
|
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|
be O |
|
divided O |
|
into O |
|
three O |
|
evolutionary O |
|
lineages O |
|
I O |
|
, O |
|
II O |
|
and O |
|
III O |
|
. O |
|
|
|
A O |
|
manual O |
|
genome O |
|
annotation O |
|
analysis O |
|
identified O |
|
this O |
|
as O |
|
the O |
|
only O |
|
type O |
|
III O |
|
PKS O |
|
gene O |
|
cluster O |
|
in O |
|
the O |
|
genome O |
|
, O |
|
consistent O |
|
with O |
|
the O |
|
antiSMASH O |
|
results O |
|
. O |
|
|
|
Puwainaphycin O |
|
F O |
|
( O |
|
4-methyl-Ahtea-PUW-F O |
|
) O |
|
, O |
|
together O |
|
with O |
|
the O |
|
congener O |
|
of O |
|
m/z O |
|
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|
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|
were O |
|
found O |
|
to O |
|
be O |
|
dominant O |
|
based O |
|
on O |
|
UV O |
|
and O |
|
MS O |
|
detection O |
|
, O |
|
other O |
|
variants O |
|
were O |
|
observed O |
|
in O |
|
trace O |
|
amounts O |
|
based O |
|
on O |
|
their O |
|
MS O |
|
signals O |
|
( O |
|
Figure O |
|
3B O |
|
) O |
|
. O |
|
|
|
Furthermore O |
|
, O |
|
a O |
|
mutation O |
|
was O |
|
detected O |
|
in O |
|
plnF O |
|
structural O |
|
gene O |
|
which O |
|
has O |
|
contributed O |
|
to O |
|
a O |
|
longer O |
|
bacteriocin O |
|
peptide O |
|
. O |
|
|
|
|