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

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

  • J Nat Prod. 2018 Nov 26;81(11):2560-2566. doi: 10.1021/acs.jnatprod.8b00720.
Muhammad Abbas 1 2 3,  Sherif I Elshahawi 1 2 4,  Xiachang Wang 1 2 5,  Larissa V Ponomareva 1 2,  Imran Sajid 3,  Khaled A Shaaban 1 2,  Jon S Thorson 1 2
Affiliations

Affiliations

  • 1 Center for Pharmaceutical Research and Innovation, College of Pharmacy , University of Kentucky , Lexington , Kentucky 40536 , United States.
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy , University of Kentucky , Lexington , Kentucky 40536 , United States.
  • 3 Department of Microbiology and Molecular Genetics , University of the Punjab , Quid-i-Azam Campus , Lahore 54590 , Pakistan.
  • 4 Department of Biomedical and Pharmaceutical Sciences , Chapman University School of Pharmacy , Irvine , California 92618 , United States.
  • 5 Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, College of Pharmacy , Nanjing University of Chinese Medicine , Nanjing 210023 , People's Republic of China.
PMID: 30418763 DOI: 10.1021/acs.jnatprod.8b00720
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.

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