Biosynthesis of merochlorins - A novel class of highly active halogenated polyketide antibiotics from marine Streptomyces sp.
Final Report Abstract
During my DFG-funded research at the Scripps Institution of Oceanography under the mentorship of Prof. Bradley Moore, I accomplished the main research goals of my proposal and successfully illuminated the biosynthesis of the highly potent and structurally complex merochlorin antibiotics produced by marine streptomycetes. I functionally assigned and characterized all involved enzymes, which eventually allowed the full in vitro reconstitution of the pathway and thus the total enzymatic synthesis of merochlorin A and B. This biosynthetic route features the formation of a novel, branched sesquiterpene that is condensed with the polyketidic precursor, thereby setting the stage for subsequent chlorination and cyclization reactions that give rise to the merochlorins. As a side project during my funding period, I investigated the central step in the biosynthesis of enterocin, another polyketide antibiotic from marine Streptomycetes. During the course of this work, previously unrecognized flavin enzymology was discovered, which facilitates an unprecedented oxidative electrocyclization reaction that is key to the formation of enterocin.
Publications
- Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement. Nature, 2013, 503, 552-556
Robin Teufel, Akimasa Miyanaga, Quentin Michaudel, Frederick Stull, Gordon Louie, Joseph P. Noel, Phil Baran, Bruce Palfey, & Bradley S. Moore
- A Multitasking Vanadium-Dependent Chloroperoxidase as an Inspiration for the Chemical Synthesis of the Merochlorins. Angew. Chem. Int. Ed., 2014
Stefan Diethelm, Robin Teufel, Leonard Kaysser, & Bradley S. Moore
(See online at https://doi.org/10.1002/anie.201405696) - One-pot Enzymatic Synthesis of Merochlorin A and B. Angew. Chem. Int. Ed., 2014
obin Teufel, Leonard Kaysser, Matthew T. Villaume, Stefan Diethelm, Mary K. Carbullido, Phil S. Baran, & Bradley S. Moore
(See online at https://doi.org/10.1002/anie.201405694)
