Natalamycin A, an Ansamycin from a Termite-AssociatedStreptomycessp.
We report a preliminary functional and complete structural characterization of a highly unusual geldanamycin analog, natalamycin A, that was isolated fromStreptomycesstrain M56 recovered from a South African nest ofMacrotermes natalensistermites. 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.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, United States of America.
Ki Hyun
KH
Kim
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, United States of America.
Timothy R
TR
Ramadhar
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, United States of America.
Christine
C
Beemelmanns
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, United States of America.
Shugeng
S
Cao
Department of Bacteriology, University of Wisconsin-Madison, 6145 Microbial Science Building, 1550 Linden Drive, Madison, Wisconsin, 53706, United States of America.
Michael
M
Poulsen
Department of Bacteriology, University of Wisconsin-Madison, 6145 Microbial Science Building, 1550 Linden Drive, Madison, Wisconsin, 53706, United States of America.
Cameron R
CR
Currie
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, United States of America.
Jon
J
Clardy