Genome-Driven Discovery of Hygrocins in Streptomyces rapamycinicus
Manar Magdy Mahmoud Mohamed1, Zhijie Yang1, Kah Yean Lum1
1Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark.
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.
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