The active conformation of avilamycin A is conferred by AviX12, a radical AdoMet enzyme

The Journal of Biological Chemistry
Raija BollA Bechthold

Abstract

The antibiotic avilamycin A is produced by Streptomyces viridochromogenes Tü57. Avilamycin belongs to the family of orthosomycins with a linear heptasaccharide chain linked to a terminal dichloroisoeverninic acid as aglycone. The gene cluster for avilamycin biosynthesis contains 54 open reading frames. Inactivation of one of these genes, namely aviX12, led to the formation of a novel avilamycin derivative named gavibamycin N1. The structure of the new metabolite was confirmed by mass spectrometry (MS) and NMR analysis. It harbors glucose as a component of the heptasaccharide chain instead of a mannose moiety in avilamycin A. Antibacterial activity tests against a spectrum of Gram-positive organisms showed that the new derivative possesses drastically decreased biological activity in comparison to avilamycin A. Thus, AviX12 seems to be implicated in converting avilamycin to its bioactive conformation by catalyzing an unusual epimerization reaction. Sequence comparisons grouped AviX12 in the radical S-adenosylmethionine protein family. AviX12 engineered with a His tag was overexpressed in Escherichia coli and purified by affinity chromatography. The iron sulfur cluster [Fe-S] present in radical AdoMet enzymes was detected in puri...Continue Reading

References

Dec 16, 1983·Biochemical and Biophysical Research Communications·M RanceK Wüthrich
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Dec 20, 2000·Antimicrobial Agents and Chemotherapy·P M McNicholasT A Black
Mar 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·L BelovaA S Mankin
Oct 18, 2002·Antimicrobial Agents and Chemotherapy·Christine B Kofoed, Birte Vester
Oct 19, 2004·Chemistry & Biology·Gabriele WeitnauerAndreas Bechthold

❮ Previous
Next ❯

Citations

Jun 23, 2016·Proceedings of the National Academy of Sciences of the United States of America·Stefan ArenzDaniel N Wilson
Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Miri KrupkinAda Yonath
Dec 6, 2008·Angewandte Chemie·Christopher J ThibodeauxHung-wen Liu
Mar 1, 2008·Critical Reviews in Biochemistry and Molecular Biology·Perry A FreyFrank J Ruzicka
Jun 3, 2014·Natural Product Reports·Emilianne K McCranie, Brian O Bachmann
May 15, 2021·ACS Chemical Biology·Carolyn E SuhAlison E Wendlandt
Jul 3, 2021·Marine Drugs·Jian-Lin XuYong Wang
Jan 31, 2014·Chemical Reviews·Joan B BroderickEric M Shepard
Sep 18, 2014·Journal of the American Chemical Society·Fumitaka KudoTadashi Eguchi

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.