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Published on: January 7, 2022
Precursor-directed biosynthesis of micacocidin derivatives with activity against Mycoplasma pneumoniae
Martin F Kreutzer1, Hirokazu Kage, Jennifer Herrmann
1Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Adolf-Reichwein-Str. 23, D-07745 Jena, Germany. markus.nett@hki-jena.de.
Abstract:
Micacocidin is a promising natural product for the treatment of Mycoplasma pneumoniae infections. In the biosynthesis of this antibiotic, a fatty acid-AMP ligase (FAAL) activates the starter unit hexanoic acid as acyl-adenylate and forwards it to an iteratively acting polyketide synthase. Biochemical analysis of the FAAL revealed an extended substrate tolerance, thereby opening the door for the modification of a micacocidin residue that is barely accessible via semisynthesis. A total of six new analogues were generated by precursor-directed biosynthesis in this study and profiled against M. pneumoniae.
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