Protein: Phenolphthiocerol/phthiocerol polyketide synthase subunit E (EC 2.3.1.292) ((Phenol)carboxyphthiodiolenone synthase subunit E) (Beta-ketoacyl-acyl-carrier-protein synthase I) (Phthiocerol synthesis polyketide synthase type I PpsE) (P9WQE1)
Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Function: Part of the PpsABCDE complex involved in the biosynthesis of the lipid core common to phthiocerols and phenolphthiocerols by successive additions of malonyl-CoA or methylmalonyl-CoA extender units. PpsA can accept as substrate the activated forms of either icosanoyl (C20), docosanoyl (C22) or lignoceroyl (C24) groups from FadD26, or a (4-hydroxyphenyl)-C17 or (4-hydroxyphenyl)-C19 fatty acyl from FadD29. PpsA initiates the biosynthesis and extends its substrate using a malonyl-CoA extender unit. The PpsB and PpsC proteins add the second and third malonyl-CoA extender units. PpsD adds an (R)-methylmalonyl unit and PpsE adds a second (R)-methylmalonyl unit. The incorporation of the methylmalonyl units results in formation of two branched methyl groups in the elongated product.
Sequence: MSIPENAIAVVGMAGRFPGAKDVSAFWSNLRRGKESIVTLSEQELRDAGVSDKTLADPAYVRRAPLLDGIDEFDAGFFGFPPLAAQVLDPQHRLFLQCAWHALEDAGADPARFDGSIGVYGTSSPSGYLLHNLLSHRDPNAVLAEGLNFDQFSLFLQNDKDFLATRISHAFNLRGPSIAVQTACSSSLVAVHLACLSLLSGECDMALAGGSSLCIPHRVGYFTSPGSMVSAVGHCRPFDVRADGTVFGSGVGLVVLKPLAAAIDAGDRIHAVIRGSAINNDGSAKMGYAAPNPAAQADVIAEAHAVSGIDSSTVSYVECHGTGTPLGDPIEIQGLRAAFEVSQTSRSAPCVLGSVKSNIGHLEVAAGIAGLIKTILCLKNKALPATLHYTSPNPELRLDQSPFVVQSKYGPWECDGVRRAGVSSFGVGGTNAHVVLEEAPAEASEVSAHAEPAGPQVILLSAQTAAALGESRTALAAALETQDGPRLSDVAYTLARRRKHNVTMAAVVHDREHAATVLRAAEHDNVFVGEAAHDGEHGDRADAAPTSDRVVFLFPGQGAQHVGMAKGLYDTEPVFAQHFDTCAAGFRDETGIDLHAEVFDGTATDLERIDRSQPALFTVEYALAKLVDTFGVRAGAYIGYSTGEYIAATLAGVFDLQTAIKTVSLRARLMHESPPGAMVAVALGPDDVTQYLPPEVELSAVNDPGNCVVAGPKDQIRALRQRLTEAGIPVRRVRATHAFHTSAMDPMLGQFQEFLSRQQLRPPRTPLLSNLTGSWMSDQQVVDPASWTRQISSPIRFADELDVVLAAPSRILVEVGPGGSLTGSAMRHPKWSTTHRTVRLMRHPLQDVDDRDTFLRALGELWSAGVEVDWTPRRPAVPHLVSLPGYPFARQRHWVEPNHTVWAQAPGANNGSPAGTADGSTAATVDAARNGESQTEVTLQRIWSQCLGVSSVDRNANFFDLGGDSLMAISIAMAAANEGLTITPQDLYEYPTLASLTAAVDASFASSGLAKPPEAQANPAVPPNVTYFLDRGLRDTGRCRVPLILRLDPKIGLPDIRAVLTAVVNHHDALRLHLVGNDGIWEQHIAAPAEFTGLSNRSVPNGVAAGSPEERAAVLGILAELLEDQTDPNAPLAAVHIAAAHGGPHYLCLAIHAMVTDDSSRQILATDIVTAFGQRLAGEEITLEPVSTGWREWSLRCAALATHPAALDTRSYWIENSTKATLWLADALPNAHTAHPPRADELTKLSSTLSVEQTSELDDGRRRFRRSIQTILLAALGRTIAQTVGEGVVAVELEGEGRSVLRPDVDLRRTVGWFTTYYPVPLACATGLGALAQLDAVHNTLKSVPHYGIGYGLLRYVYAPTGRVLGAQRTPDIHFRYAGVIPELPSGDAPVQFDSDMTLPVREPIPGMGHAIELRVYRFGGSLHLDWWYDTRRIPAATAEALERTFPLALSALIQEAIAAEHTEHDDSEIVGEPEAGALVDLSSMDAG
InterPro domains: - IPR020841: Polyketide synthase, beta-ketoacyl synthase domain (domain) [5-441]
- IPR020806: Polyketide synthase-like, phosphopantetheine-binding domain (domain) [936-1004]
- IPR018201: Beta-ketoacyl synthase, active site (active_site) [175-191]
- IPR016035: Acyl transferase/acyl hydrolase/lysophospholipase (homologous_superfamily) [549-830]
- IPR014030: Beta-ketoacyl synthase-like, N-terminal (domain) [6-261]
- IPR036736: ACP-like superfamily (homologous_superfamily) [920-1006]
- IPR014031: Beta-ketoacyl synthase, C-terminal (domain) [270-389]
- IPR023213: Chloramphenicol acetyltransferase-like domain superfamily (homologous_superfamily) [1014-1188]
- IPR050091: Polyketide and Nonribosomal Peptide Biosynthesis Enzymes (family) [8-910]
- IPR032821: Polyketide synthase, C-terminal extension (domain) [392-500]
- IPR014043: Acyl transferase domain (domain) [551-864]
- IPR009081: Phosphopantetheine binding ACP domain (domain) [930-1004]
- IPR001242: Condensation domain (domain) [1027-1358]
- IPR016036: Malonyl-CoA ACP transacylase, ACP-binding (homologous_superfamily) [675-733]
- IPR001227: Acyl transferase domain superfamily (homologous_superfamily) [551-851]
- IPR016039: Thiolase-like (homologous_superfamily) [3-461]
Interaction partners: - Phenolphthiocerol/phthiocerol polyketide synthase subunit C
- Phenolphthiocerol/phthiocerol polyketide synthase subunit D
- Doxorubicin resistance ATP-binding protein DrrA
- Phthiocerol/phthiodiolone dimycocerosyl transferase
- Phenolphthiocerol/phthiocerol polyketide synthase subunit A
- Phenolphthiocerol/phthiocerol polyketide synthase subunit B
- Doxorubicin resistance ABC transporter permease protein DrrB
- Long-chain-fatty-acid--AMP ligase FadD26
- Probable doxorubicin resistance ABC transporter permease protein DrrC
- Thioesterase TesA
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0036094 (small molecule binding), GO:0033218 (amide binding), GO:0016740 (transferase activity), GO:0072341 (modified amino acid binding), GO:0005515 (protein binding), GO:0019842 (vitamin binding), GO:0042802 (identical protein binding), GO:0016746 (acyltransferase activity), GO:0016747 (acyltransferase activity, transferring groups other than amino-acyl groups)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0071840 (cellular component organization or biogenesis), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0071554 (cell wall organization or biogenesis), GO:0044238 (primary metabolic process), GO:0044255 (cellular lipid metabolic process), GO:0044249 (cellular biosynthetic process), GO:0016043 (cellular component organization), GO:1901576 (organic substance biosynthetic process), GO:0044085 (cellular component biogenesis), GO:0006629 (lipid metabolic process), GO:0042546 (cell wall biogenesis), GO:1901135 (carbohydrate derivative metabolic process), GO:0009273 (peptidoglycan-based cell wall biogenesis), GO:1903509 (liposaccharide metabolic process), GO:1901137 (carbohydrate derivative biosynthetic process), GO:0046467 (membrane lipid biosynthetic process), GO:0008610 (lipid biosynthetic process), GO:0006643 (membrane lipid metabolic process), GO:0022607 (cellular component assembly), GO:0009247 (glycolipid biosynthetic process), GO:0006664 (glycolipid metabolic process), GO:0071766 (Actinobacterium-type cell wall biogenesis)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0071944 (cell periphery), GO:0016020 (membrane), GO:0030312 (external encapsulating structure), GO:0005618 (cell wall), GO:0005886 (plasma membrane), GO:0009274 (peptidoglycan-based cell wall)