Abstract
Rebeccamycin and staurosporine represent two broad classes of indolocarbazole glycoside natural products with antitumor properties. Based upon previous sequence annotation and in vivo studies, rebG encodes for the rebeccamycin N-glucosyltransferase, and rebM for the requisite 4′-O-methyltransferase. In the current study, an efficient in vivo biotransformation system for RebG was established in both Streptomyces lividans and Escherichia coli. Bioconversion experiments revealed RebG to glucosylate a set of indolocarbazole surrogates, the products of which could be further modified by in vitro RebM-catalyzed 4′-O-methylation. Both RebG and RebM displayed substrate promiscuity, and evidence for a remarkable lack of RebG regioselectivity in the presence of asymmetric substrates is also provided. In the context of the created indolocarbazole analogues, cytotoxicity assays also highlight the importance of 4′-O-methylotion for their biological activity.
Original language | English (US) |
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Pages (from-to) | 795-804 |
Number of pages | 10 |
Journal | ChemBioChem |
Volume | 7 |
Issue number | 5 |
DOIs | |
State | Published - May 2006 |
Externally published | Yes |
Keywords
- Biosynthesis
- Glycosylation
- Methylation
- Rebeccamycin
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Organic Chemistry