Reaction: 4-nitrobenzoyl-CoA + malonyl-CoA + 4 (S)-methylmalonyl-CoA + 4 NADPH + 4 H+ = demethylluteothin + 5 CO2 + 6 CoA + 4 NADP+ + 3 H2O
For diagram of reaction, click here
Glossary: demethylluteothin = nordeoxyaureothin = 2-[(3E,5E)-3,5-dimethyl-6-(4-nitrophenyl)hexa-3,5-dien-1-yl]-6-hydroxy-3,5-dimethyl-4H-pyran-4-one
aureothin = 2-methoxy-3,5-dimethyl-6-[(2R,4Z)-4-[(2E)-2-methyl-3-(4-nitrophenyl)prop-2-en-1-ylidene]oxolan-2-yl]-4H-pyran-4-one
Other name(s): aurABC (gene names); aureothin polyketide synthase complex
Systematic name: malonyl-CoA/(S)-methylmalonyl-CoA:4-nitrobenzoyl-CoA (methyl)malonyltransferase (demethylluteothin-forming)
Comments: This polyketide synthase, characterized from the bacterium Streptomyces thioluteus, generates the backbone of the antibiotic aureothin. It is composed of 4 modules that total 18 domains and is encoded by three genes. The enzyme accepts the unusual starter unit 4-nitrobenzoyl-CoA and extends it by 4 molecules of (S)-methylmalonyl-CoA and a single molecule of malonyl-CoA. The first module (encoded by aurA) is used twice in an iterative fashion, so that the five Claisen condensation reactions are catalysed by only four modules. The iteration becomes possible by the transfer of the [acp]-bound polyketide intermediate back to the ketosynthase (KS) domain on the opposite polyketide synthase strand (polyketides are homodimeric).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. He, J. and Hertweck, C. Iteration as programmed event during polyketide assembly; molecular analysis of the aureothin biosynthesis gene cluster. Chem. Biol. 10 (2003) 1225-1232. [PMID: 14700630]
2. He, J. and Hertweck, C. Functional analysis of the aureothin iterative type I polyketide synthase. Chembiochem 6 (2005) 908-912. [PMID: 15812854]
3. Busch, B., Ueberschaar, N., Sugimoto, Y. and Hertweck, C. Interchenar retrotransfer of aureothin intermediates in an iterative polyketide synthase module. J. Am. Chem. Soc. 134 (2012) 12382-12385. [PMID: 22799266]