Irumamycin

1. Discovery, producing organism and structures1-4)
Antifungal screening led to the discovery of the irumamycins from a culture broth of Streptomyces subflavus. Subsequently, a blocked mutant of the strain AM-3603T was found to accumulate
two lactones, named irumanolides I and II.

CH3 CH3 CH3 CH3
R1O

R2
H3COH OO

OOH

Streptomyces subflavus subsp.
irumaensis AM-3603T
3'-O-Decarbamoylirumamycin

Irumamycin
OH

R1

R2

H2NCOO

H3C

CH3HOCH3OO

CH3CH3O

Irumanolide IIHHCH3CH3OHCH3OOIrumanolide ICH3OCH3OCH3OHO

2. Physical data (Irumamycin)
White amorphous powder. C41H65NO12; mol wt 763.45. Sol. in MeOH, EtOH, acetone. Insol. in
H2O, hexane, petroleum ether.

3. Biological activity5)
1) Antifungal activity

MIC (µg/ml)*1
Test organism		
Iruma- Venturi- Botry- Aabo- Blasti- Prumycin		
mycin cidin A6) cidin mycin A cidin S
Pyricularia oryzae
A*2
0.05
>0.03
0.05
<0.2 >100>100
B>0.03>0.03
0.03<0.225100
Sclerotinia cinerea
A0.05
0.780.4
0.250
1.56
B
0.1
0.78
0.78
0.2
25
6.25
Rhizoctonia solani
A0.4
1.56
12.5
>100>100>100B
25>25>25>100>100>100
Botrytis cinerea
A—*3——>10050>100
B
6.25 >25
12.5>100
10050
Alternaria kikuchiana A50——>10050>100B
12.55
12.5
100
12.5
50
*1 Glucose-potato agar, 2–3 days.
*2 A, isolated from an infected plant; B, laboratory stock culture.
*3 —, Not tested.

2) Protective effect against plant-pathogenic fungi
Protection of plants from fungal infection by irumamycin in pot tests
Pathogenic organism
Plant infected Irumamycin Protection		(ppm)
value (%)
Botrytis cinerea
Cucumber				
Colletotrichum lagenarium
Cucumber				Cochliobolus miyabeanus
Rice plant

20010050200
10050200989797
100999292

Calculated from an equation:

1–

No. of infectious lesions on treated plants
No. of infectious lesions on control plants

X 1003) Antitrypanosomal activities8)
In the course of our screening program to discover new antitrypanosomal antibiotics, by screening metabolites from soil microorganisms, we have discovered 10 compounds that display potent antitrypanosomal activity in vitro. We reported the results of sensitivity tests on the GUTat
3.1 strain of T. b. brucei and the STIB900 strain of T. b. rhodesiense using the four commonlyused antitrypanosomal drugs as well as detailing the novel antitrypanosomal activity and cytotoxicity of the ten antibiotics in vitro.

In vitro antitrypanosomal activity and cytotoxicity of 10 microbial metabolites
IC50 (ng/mL)
CompoundAntitrypanosomal activity
GUTat 3.1

Aureothin
Cellocidin
Destomycin A
Echinomycin
Hedamycin
Irumamycin
LL-Z 1272b
O -methylnanaomycin AVenturicidin AVirustomycin A1.4150
330
20142049210
1200.45

GUTat 3.1: Trypanosoma brucei brucei strain
STIB900: Trypanosoma brucei rhodesiense strain
MRC-5: Human lung fibroblast cell line

STIB900

Cytotoxicity MRC5

MRC-5/ GUTat 3.1

MRC-5/STIB900

1.1
30
210
14183159
16540
480>25,000
5,910
21,140
6,310>25,000>12,500
13,6204,890>25,000
80>17,857
39
64
316>1,786>625
278
23>208178>22,727
179
101451>1,389>403
231
306>1850.2Selective index

4. Biosynthesis4,7)
The carbon skeleton of the aglycone moiety originated from 5 acetate and 8 propionate units.
The biosynthetic pathway to irumamycin was proposed as shown below:O

5 X acetate
8 X propionate

O

CH3COOH
CH3CH2COOH

Irumamycin

Rhamnose

NH2-CO

Irumanolide I

Irumanolide II

epoxidation

5. References
1. [228] S. Ōmura et al., J. Antibiot. 35, 256-257 (1982)
2. [257] S. Ōmura et al., J. Org. Chem. 47, 5413-5415 (1982)
3. [329] A. Nakagawa et al., J. Antibiot. 38, 1266-1269 (1985)
4. [265] N. Sadakane et al., J. Antibiot. 36, 931-933 (1983)
5. [302] S. Ōmura et al., J. Antibiot. 37, 1572-1578 (1984)
6. 		
M. Brufani et al., Experientia 27, 604 (1971)
7. [253] S. Ōmura et al., In “Trends in Antibiotic Research” pp.135-145, Japan Antibiotics
Res. Assoc. (1982)
8. [993] K. Otoguro et al., J. Antibiot. 61, 372-378 (2008)