Homodimericin A: A Complex Hexacyclic Fungal Metabolite

Citation:

Mevers E, Saurí J, Liu Y, Moser A, Ramadhar TR, Varlan M, Williamson TR, Martin GE, Clardy J. Homodimericin A: A Complex Hexacyclic Fungal Metabolite. J Am Chem Soc 2016;138(38):12324-7.

Date Published:

2016 09 28

Abstract:

Microbes sense and respond to their environment with small molecules, and discovering these molecules and identifying their functions informs chemistry, biology, and medicine. As part of a study of molecular exchanges between termite-associated actinobacteria and pathogenic fungi, we uncovered a remarkable fungal metabolite, homodimericin A, which is strongly upregulated by the bacterial metabolite bafilomycin C1. Homodimericin A is a hexacyclic polyketide with a carbon backbone containing eight contiguous stereogenic carbons in a C20 hexacyclic core. Only half of its carbon atoms have an attached hydrogen, which presented a significant challenge for NMR-based structural analysis. In spite of its microbial production and rich stereochemistry, homodimericin A occurs naturally as a racemic mixture. A plausible nonenzymatic reaction cascade leading from two identical achiral monomers to homodimericin A is presented, and homodimericin A's formation by this path, a six-electron oxidation, could be a response to oxidative stress triggered by bafilomycin C1.

Last updated on 04/08/2022