Identification of neuroprotective spoxazomicin and oxachelin glycosides via chemoenzymatic glycosyl-scanning

Jianjun Zhang, Ryan R. Hughes, Meredith A. Saunders, Sherif I. Elshahawi, Larissa V. Ponomareva, Yinan Zhang, Sydney R. Winchester, Samantha A. Scott, Manjula Sunkara, Andrew J. Morris, Mark A. Prendergast, Khaled A. Shaaban, Jon S. Thorson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The assessment of glycosyl-scanning to expand the molecular and functional diversity of metabolites from the underground coal mine fire-associated Streptomyces sp. RM-14- 6 is reported. Using the engineered glycosyltransferase OleD Loki and a 2-chloro-4-nitrophenylglycoside-based screen, six metabolites were identified as substrates of OleD Loki, from which 12 corresponding metabolite glycosides were produced and characterized. This study highlights the first application of the 2-chloro-4-nitrophenylglycoside-based screen toward an unbiased set of unique microbial natural products and the first reported application of the 2-chloro-4-nitrophenylglycosidebased transglycosylation reaction for the corresponding preparative synthesis of target glycosides. Bioactivity analysis (including antibacterial, antifungal, anticancer, and EtOH damage neuroprotection assays) revealed glycosylation to attenuate the neuroprotective potency of 4, while glycosylation of the structurally related inactive spoxazomicin C (3) remarkably invoked neuroprotective activity.

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalJournal of Natural Products
Volume80
Issue number1
DOIs
StatePublished - Jan 27 2017

Bibliographical note

Funding Information:
This work was supported in part by NIH R37 AI52188, NIH T32 DA016176 (YZ), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, and the National Center for Advancing Translational Sciences (UL1TR001998).

Publisher Copyright:
© 2016 American Chemical Society and American Society of Pharmacognosy.

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Identification of neuroprotective spoxazomicin and oxachelin glycosides via chemoenzymatic glycosyl-scanning'. Together they form a unique fingerprint.

Cite this