Kim, Ki Hyun2; Ramadhar, Timothy R.2; Beemelmanns, Christine2; Cao, Shugeng2; Thomas-Poulsen, Michael4; Currie, Cameron R.3; Clardy, Jon2
1 Ecology and Evolution, Department of Biology, Faculty of Science, Københavns Universitet2 Harvard Medical School3 University of Wisconsin-Madison4 Ecology and Evolution, Department of Biology, Faculty of Science, Københavns Universitet
We report a preliminary functional and complete structural characterization of a highly unusual geldanamycin analog, natalamycin A, that was isolated from Streptomyces strain M56 recovered from a South African nest of Macrotermes natalensis termites. Bioassay-guided fractionation based on antifungal activity led to the isolation of natalamycin A, and a combination of NMR spectroscopy and X-ray crystallographic analysis, including highly-accurate quantum-chemical NMR calculations on the largest and most conformationally-flexible system to date, revealed natalamycin A's three-dimensional solid- and solution-state structure. This structure along with the structures of related compounds isolated from the same source suggest a geldanamycin-like biosynthetic pathway with unusual post-PKS modifications.