Puromycins B–E, Naturally Occurring Amino-Nucleosides Produced by the Himalayan Isolate Streptomyces sp. PU-14G

Document Type

Article

Publication Date

11-12-2018

Abstract

The isolation and structure elucidation of four new naturally occurring amino-nucleoside [puromycins B–E (1–4)] metabolites from a Himalayan isolate (Streptomyces sp. PU-14-G, isolated from the Bara Gali region of northern Pakistan) is reported. Consistent with prior reports, comparative antimicrobial assays revealed the need for the free 2″-amine for anti-Gram-positive bacteria and antimycobacterial activity. Similarly, comparative cancer cell line cytotoxicity assays highlighted the importance of the puromycin-free 2″-amine and the impact of 3′-nucleoside substitution. These studies extend the repertoire of known naturally occurring puromycins and their corresponding SAR. Notably, 1 represents the first reported naturally occurring bacterial puromycin-related metabolite with a 3′-N-amino acid substitution that differs from the 3′-N-tyrosinyl of classical puromycin-type natural products. This discovery suggests the biosynthesis of 1 in Streptomyces sp. PU-14G may invoke a uniquely permissive amino-nucleoside synthetase and/or multiple synthetases and sets the stage for further studies to elucidate, and potentially exploit, new biocatalysts for puromycin chemoenzymatic diversification.

Comments

This article was originally published in Journal of Natural Products, volume 81, issue 11, in 2018. https://doi.org/10.1021/acs.jnatprod.8b00720

Copyright

American Chemical Society and American Society of Pharmacognosy

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