Journal article

Publication year: 2015

Pages: 6525-6536

Journal: Chemical Science

Volume number: 6

Issue number: 11

ISSN: 2041-6520

DOI Link: https://doi.org/10.1039/c5sc02488a

Publisher: Royal Society of Chemistry

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.

Harvard Citation style: Zocher, G., Vilstrup, J., Heine, D., Hallab, A., Goralski, E., Hertweck, C., et al. (2015) Structural basis of head to head polyketide fusion by CorB, Chemical Science, 6(11), pp. 6525-6536. https://doi.org/10.1039/c5sc02488a

APA Citation style: Zocher, G., Vilstrup, J., Heine, D., Hallab, A., Goralski, E., Hertweck, C., Stahl, M., Schäberle, T., & Stehle, T. (2015). Structural basis of head to head polyketide fusion by CorB. Chemical Science. 6(11), 6525-6536. https://doi.org/10.1039/c5sc02488a