Structural basis of head to head polyketide fusion by CorB. Issue 11 (17th August 2015)

• Record Type: Journal Article
• Authors: Zocher, Georg; Vilstrup, Joachim; Heine, Daniel; Hallab, Asis; Goralski, Emilie; Hertweck, Christian; Stahl, Mark; Schäberle, Till F.; Stehle, Thilo
• Is Part Of: Chemical science. Volume 6:Issue 11(2015:Nov.)
• Page Start: 6525
• Page End: 6536
• Publication Date: 2015-08-17
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5sc02488a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Corallopyronin A is a polyketide derived from the myxobacterium Corallococcus coralloides with potent antibiotic features. Abstract : Corallopyronin A is a polyketide derived from the myxobacterium Corallococcus coralloides with potent antibiotic features. The gene cluster responsible for the biosynthesis of corallopyronin A has been described recently, and it was proposed that CorB acts as a ketosynthase to interconnect two polyketide chains in a rare head-to-head condensation reaction. We determined the structure of CorB, the interconnecting polyketide synthase, to high resolution and found that CorB displays a thiolase fold. Site-directed mutagenesis showed that the catalytic triad consisting of a cysteine, a histidine and an asparagine is crucial for catalysis, and that this triad shares similarities with the triad found in HMG-CoA synthases. We synthesized a substrate mimic to derivatize purified CorB and confirmed substrate attachment by ESI-MS. Structural analysis of the complex yielded an electron density-based model for the polyketide chain and showed that the unusually wide, T-shaped active site is able to accommodate two polyketides simultaneously. Our structural analysis provides a platform for understanding the unusual head-to-head polyketide-interconnecting reaction catalyzed by CorB.