UniProt functional annotation for Q03133



	UniProt functional annotation for Q03133

UniProt code: Q03133.

Organism: Saccharopolyspora erythraea (Streptomyces erythraeus).

Taxonomy: Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae; Saccharopolyspora.

Function: Involved in the biosynthesis of antibiotic erythromycin via the biosynthesis of its aglycone precursor, 6-deoxyerythronolide B (6- dEB). {ECO:0000269|PubMed:21095573, ECO:0000305|PubMed:17328673}.

Catalytic activity: Reaction=6 (S)-methylmalonyl-CoA + 12 H(+) + 6 NADPH + propanoyl-CoA = 6-deoxyerythronolide B + 6 CO2 + 7 CoA + H2O + 6 NADP(+); Xref=Rhea:RHEA:23068, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16089, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57327, ChEBI:CHEBI:57392, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=2.3.1.94; Evidence={ECO:0000269|PubMed:21095573};

Cofactor: Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942; Evidence={ECO:0000305|PubMed:16844787}; Note=Binds 2 phosphopantetheines covalently. {ECO:0000305};

Activity regulation: Inhibited by diphenyl phosphonates derivatives such as diphenyl allylphosphonate. {ECO:0000269|PubMed:26592346}.

Pathway: Antibiotic biosynthesis; erythromycin biosynthesis. {ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:21095573}.

Subunit: Homodimer (PubMed:11752428, PubMed:12379102, PubMed:16844787). Erythronolide synthase is composed of EryAI, EryAII and EryAIII multimodular (2 modules) polypeptides each coding for a functional synthase subunit which participates in 2 of the six FAS-like elongation steps required for formation of the polyketide. Module 1, 2, 3, 4, 5, and 6 participating in biosynthesis steps 1, 2, 3, 4, 5, and 6, respectively. {ECO:0000269|PubMed:11752428, ECO:0000269|PubMed:12379102, ECO:0000269|PubMed:16844787, ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:1740151, ECO:0000305|PubMed:2024119}.

Miscellaneous: Type I modular polyketide synthases (PKSs) catalyze the step-wise condensation of simple carboxylic acid derivatives. Organizationally, type I PKSs are arranged into modules, wherein each module is comprised of a set of catalytic activities that is responsible for a single elongation of the polyketide chain and the appropriate reductive processing of the beta-keto functionality. A minimal elongation module contains an acyl transferase (AT) domain, an acyl-carrier protein (ACP) domain, and a ketosynthase (KS) domain. The AT domain is responsible for loading the methylmalonyl-CoA extender unit onto the phosphopantetheinylated ACP domain. Subsequently, the KS domain decarboxylates and then condenses the ACP-bound extender unit with the growing polyketide chain obtained from the preceding module to yield an ACP-bound beta-ketoacyl intermediate. In addition to the three core domains, each elongation module may contain up to three additional domains: a ketoreductase (KR), dehydratase (DH), and an enoyl reductase (ER) that are responsible for the reductive processing of the beta-keto functionality prior to the next extension step. The presence of a KR domain alone gives rise to a beta-hydroxyl functionality, the presence of both a KR and a DH domain generates an alkene, while the combination of KR, DH, and ER results in complete reduction to the alkane. Finally, a thioesterase (TE) domain, typically found at the terminus of the last elongation module, catalyzes the termination of polyketide biosynthesis. The activity of this domain results in cleavage of the acyl chain from the adjacent ACP and formation of the macrocyclic ring. {ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:21095573}.

Annotations taken from UniProtKB at the EBI.


Organism:		Saccharopolyspora erythraea (Streptomyces erythraeus).
Taxonomy:		Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae; Saccharopolyspora.



Function:		Involved in the biosynthesis of antibiotic erythromycin via the biosynthesis of its aglycone precursor, 6-deoxyerythronolide B (6- dEB). {ECO:0000269\|PubMed:21095573, ECO:0000305\|PubMed:17328673}.


Catalytic activity:		Reaction=6 (S)-methylmalonyl-CoA + 12 H(+) + 6 NADPH + propanoyl-CoA = 6-deoxyerythronolide B + 6 CO2 + 7 CoA + H2O + 6 NADP(+); Xref=Rhea:RHEA:23068, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16089, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57327, ChEBI:CHEBI:57392, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=2.3.1.94; Evidence={ECO:0000269\|PubMed:21095573};
Cofactor:		Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942; Evidence={ECO:0000305\|PubMed:16844787}; Note=Binds 2 phosphopantetheines covalently. {ECO:0000305};
Activity regulation:		Inhibited by diphenyl phosphonates derivatives such as diphenyl allylphosphonate. {ECO:0000269\|PubMed:26592346}.
Pathway:		Antibiotic biosynthesis; erythromycin biosynthesis. {ECO:0000305\|PubMed:17328673, ECO:0000305\|PubMed:21095573}.
Subunit:		Homodimer (PubMed:11752428, PubMed:12379102, PubMed:16844787). Erythronolide synthase is composed of EryAI, EryAII and EryAIII multimodular (2 modules) polypeptides each coding for a functional synthase subunit which participates in 2 of the six FAS-like elongation steps required for formation of the polyketide. Module 1, 2, 3, 4, 5, and 6 participating in biosynthesis steps 1, 2, 3, 4, 5, and 6, respectively. {ECO:0000269\|PubMed:11752428, ECO:0000269\|PubMed:12379102, ECO:0000269\|PubMed:16844787, ECO:0000305\|PubMed:17328673, ECO:0000305\|PubMed:1740151, ECO:0000305\|PubMed:2024119}.
Miscellaneous:		Type I modular polyketide synthases (PKSs) catalyze the step-wise condensation of simple carboxylic acid derivatives. Organizationally, type I PKSs are arranged into modules, wherein each module is comprised of a set of catalytic activities that is responsible for a single elongation of the polyketide chain and the appropriate reductive processing of the beta-keto functionality. A minimal elongation module contains an acyl transferase (AT) domain, an acyl-carrier protein (ACP) domain, and a ketosynthase (KS) domain. The AT domain is responsible for loading the methylmalonyl-CoA extender unit onto the phosphopantetheinylated ACP domain. Subsequently, the KS domain decarboxylates and then condenses the ACP-bound extender unit with the growing polyketide chain obtained from the preceding module to yield an ACP-bound beta-ketoacyl intermediate. In addition to the three core domains, each elongation module may contain up to three additional domains: a ketoreductase (KR), dehydratase (DH), and an enoyl reductase (ER) that are responsible for the reductive processing of the beta-keto functionality prior to the next extension step. The presence of a KR domain alone gives rise to a beta-hydroxyl functionality, the presence of both a KR and a DH domain generates an alkene, while the combination of KR, DH, and ER results in complete reduction to the alkane. Finally, a thioesterase (TE) domain, typically found at the terminus of the last elongation module, catalyzes the termination of polyketide biosynthesis. The activity of this domain results in cleavage of the acyl chain from the adjacent ACP and formation of the macrocyclic ring. {ECO:0000305\|PubMed:17328673, ECO:0000305\|PubMed:21095573}.