%0 Journal Article
%T Genome-Driven Discovery of Hygrocins in Streptomyces rapamycinicus.
%A Mahmoud Mohamed MM
%A Yang Z
%A Lum KY
%A Peschel G
%A Rosenbaum MA
%A Weber T
%A Coriani S
%A Gotfredsen CH
%A Ding L
%J J Nat Prod
%V 87
%N 5
%D 2024 May 24
%M 38647518
%F 4.803
%R 10.1021/acs.jnatprod.3c00767
%X 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.