Characterization of the TDP-D-ravidosamine biosynthetic pathway: one-pot enzymatic synthesis of TDP-D-ravidosamine from thymidine-5-phosphate and glucose-1-phosphate.

Abstract

Ravidomycin V and related compounds, e.g., FE35A-B, exhibit potent anticancer activities against various cancer cell lines in the presence of visible light. The amino sugar moieties (D-ravidosamine and its analogues, respectively) in these molecules contribute to the higher potencies of ravidomycin and analogues when compared to closely related compounds with neutral or branched sugars. Within the ravidomycin V biosynthetic gene cluster, five putative genes encoding NDP-D-ravidosamine biosynthetic enzymes were identified. Through the activities of the isolated enzymes in vitro, it is demonstrated that ravD, ravE, ravIM, ravAMT and ravNMT encode TDP-D-glucose synthase, TDP-4-keto-6-deoxy-D-glucose-4,6-dehydratase, TDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase, TDP-3-keto-6-deoxy-D-galactose-3-aminotransferase, and TDP-3-amino-3,6-dideoxy-D-galactose-N,N-dimethyl-transferase, respectively. A protocol for a one-pot enzymatic synthesis of TDP-D-ravidosamine has been developed. The results presented here now set the stage to produce TDP-D-ravidosamine routinely for glycosylation studies.

• Authors: Madan K Kharel, Hui Lian, Jürgen Rohr
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 9 Issue 6 Pg. 1799-808 (Mar 21 2011) ISSN: 1477-0539 [Electronic] England
• PMID: 21264378 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Glucosephosphates
• Nucleoside Diphosphate Sugars
• Thymine Nucleotides
• Thymidine Monophosphate
• glucose-1-phosphate

Topics

• Bacillales (enzymology)
• Escherichia coli (enzymology)
• Glucosephosphates (biosynthesis, chemistry)
• Molecular Structure
• Multigene Family
• Nucleoside Diphosphate Sugars (chemistry, metabolism)
• Salmonella typhimurium (enzymology)
• Thymidine Monophosphate (chemistry, metabolism)
• Thymine Nucleotides (chemistry)