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.
|Number of pages
|Journal of Natural Products
|Published - Jan 27 2017
Bibliographical noteFunding 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).
© 2016 American Chemical Society and American Society of Pharmacognosy.
ASJC Scopus subject areas
- Analytical Chemistry
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery
- Complementary and alternative medicine
- Organic Chemistry