Mevers, EmilySaurí, JosepLiu, YizhouMoser, ArvinRamadhar, Timothy R.Varlan, MariaWilliamson, R. ThomasMartin, Gary E.Clardy, Jon2017-11-212016Mevers, Emily, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, and Jon Clardy. 2016. “Homodimericin A: A Complex Hexacyclic Fungal Metabolite.” Journal of the American Chemical Society 138 (38): 12324-12327. doi:10.1021/jacs.6b07588. http://dx.doi.org/10.1021/jacs.6b07588.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34375281Microbes 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.en-USJournal Article2017-11-2110.1021/jacs.6b07588