Tuesday, August 14, 2012: 9:00 AM
Jefferson West, Concourse Level (Washington Hilton)
Cervimycins are tetracycline-type aromatic polyketide glycosides produced by a Streptomyces tendae strain isolated from a cave with bat dung–derived Neolithic wall paintings.1 As the cervimycins have substantial activity against a range of bacteria, including severe nosocomial pathogens such as methicillin-resistant staphylococci and vancomycin-resistant enterococci, they represent promising therapeutic agents. Notably, cervimycins differ from classical tetracyclins in their substitution pattern, which includes six trideoxyhexoses with methylmalonyl or dimethylmalonyl units attached to a terminal sugar moiety.2 Surprisingly, a ketosynthase-like enzyme, CerJ, catalyzes this rare antibiotic modification. Furthermore, a mutant deficient in the cerJ gene produces a cervimycin variant with higher antibacterial activity.3 This work not only unveils a previously undescribed role for a ketosynthase, but also serves as a starting point for protein engineering and creation of antibiotics with similar architectures.
References:
1. K. Herold, F. A. Gollmick, I. Groth, M. Roth, K.D. Menzel, U. Möllmann, U. Gräfe, C. Hertweck: Chem. Eur. J. 2005, 11, 5523-5530.
2. K. Herold, Z. Xu, F. A. Gollmick, U. Gräfe, C. Hertweck: Org. Biomol. Chem. 2004, 2, 2411-2414.
3. T. Bretschneider, G. Zocher, M. Unger, K. Scherlach, T. Stehle, C. Hertweck: Nature Chem. Biol. 2012, 8,154-161.