Glycosyltransferases are key enzymes involved in the biosynthesis of valuable natural products providing an excellent drug-tailoring tool. Herein, we report the identification of two cooperative glycosyltransferases from the sqn gene cluster directing the biosynthesis of saquayamycins in Streptomyces sp. KY40-1: SqnG1 and SqnG2. Gene inactivation of sqnG1 leads to 50-fold decrease in saquayamycin production, while inactivation of sqnG2 leads to complete production loss, suggesting that SqnG2 acts as dual O- and C-glycosyltransferase. Gene inactivation of a third putative glycosyltransferase-encoding gene, sqnG3, does not affect saquayamycin production in a major way, suggesting that SqnG3 has no or a supportive role in glycosylation. The data indicate that SqnG1 and SqnG2 are solely and possibly cooperatively responsible for the sugar diversity observed in saquayamycins 1-7. This is the first evidence of a glycosyltransferase system showing codependence to achieve dual O- and C-glycosyltransferase activity, utilizing NDP-activated d-olivose, l-rhodinose, as well as an unusual amino sugar, presumably 3,6-dideoxy-l-idosamine.
|Number of pages||6|
|Journal||ACS Chemical Biology|
|State||Published - Oct 20 2017|
Bibliographical noteFunding Information:
This study was supported by grants from the U.S. National Institutes of Health CA 091901 and GM 105977. NMR data were acquired at the Center for Environmental and Systems Biochemistry, supported by the University of Kentucky, the National Institutes of Health (NIH) 1U24DK097215-01A1 Common Funds for Metabolomics, and by National Cancer Institute (NCI) Cancer Center Support Grant (P30 CA177558).
© 2017 American Chemical Society.
ASJC Scopus subject areas
- Molecular Medicine