Details

Autor(en) / Beteiligte

• Zocher, Georg
• Vilstrup, Joachim
• Heine, Daniel
• Hallab, Asis
• Goralski, Emilie
• Hertweck, Christian
• Stahl, Mark
• Schäberle, Till F
• Stehle, Thilo

Titel

Structural basis of head to head polyketide fusion by CorB

Ist Teil von

• Chemical science (Cambridge), 2015-01, Vol.6 (11), p.6525-6536

Ort / Verlag

England

Erscheinungsjahr

2015

Quelle

Elektronische Zeitschriftenbibliothek

Beschreibungen/Notizen

• Corallopyronin A is a polyketide derived from the myxobacterium 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.