Genome-driven discovery of hygrocins in Streptomyces rapamycinicus.

Mahmoud Mohamed MM, Yang Z, Lum KY, Peschel G, Rosenbaum MA, Weber T, Coriani S, Gotfredsen CH, Ding L (2024) Genome-driven discovery of hygrocins in Streptomyces rapamycinicus. J Nat Prod 87(5), 1321-1329.

Abstract

Ansamycins, represented by the antituberculosis drug rifamycin, are an important family of natural products. To obtain new ansamycins, Streptomyces rapamycinicus IMET 43975 harboring an ansamycin biosynthetic gene cluster was fermented in a 50 L scale, and subsequent purification work led to the isolation of five known and four new analogues, where hygrocin W (2) belongs to benzoquinonoid ansamycins, and the other three hygrocins, hygrocins X-Z (6-8), are new seco-hygrocins. The structures of ansamycins (1-8) were determined by the analysis of spectroscopic (1D/2D NMR and ECD) and MS spectrometric data. The Baeyer-Villiger enzyme which catalyzed the ester formation in the ansa-ring was confirmed through in vivo CRISPR base editing. The discovery of these compounds further enriches the structural diversity of ansamycins.

Leibniz-HKI-Authors

Miriam Agler-Rosenbaum
Gundela Peschel

Identifier

doi: 10.1021/acs.jnatprod.3c00767

PMID: 38647518