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ARS Home » Midwest Area » Peoria, Illinois » National Center for Agricultural Utilization Research » Renewable Product Technology Research » Research » Publications at this Location » Publication #266031
Title: Biosynthesis of the tunicamycins: Translocase-I inhibitors that target the synthesis of bacterial peptidoglycan and eukaryotic N-glycoproteins

Author
item Price, Neil
item Bowman, Michael
item CHEN, WENQING - Wuhan University
item DENG, ZIXIN - Shanghai Jiaotong University

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/25/2011
Publication Date: 3/25/2011
Citation: Price, N.P., Bowman, M.J., Chen, W., Deng, Z. 2011. Biosynthesis of the tunicamycins: Translocase-I inhibitors that target the synthesis of bacterial peptidoglycan and eukaryotic N-glycoproteins [abstract]. University of Waterloo, Ontario, Canada, Department of Biology Seminar Series. p. 2.

Interpretive Summary:

Technical Abstract: The tunicamycins are a group of natural products that target the biosynthesis of bacterial peptidoglycan and eukaryotic N-glycoproteins. The mechanism of action is known, with the tunicamycins established as transition state analogs for hexosamine-1-phosphate:prenol phosphate translocases. Hence, this inhibits the formation of N-acetylmuramyl-undecanol pyrophosphate in bacteria or N-acetylglucosamine-dolichol pyrophosphate in eukaryotes, which are essential intermediates in these organisms. We have investigated the biosynthesis of the tunicamycins by certain streptomyces species, and have proposed a pathway in which the 11-carbon dialdose sugar, tunicamine, is derived from uridine and N-acetylglucosamine. Once formed the uridyl-tunicaminyl intermediate is a,ß-1,11-glycosylated and N-acylated to form the bioactive compounds prior to secretion. Using heterologous expression we have identified twelve tun genes (tunA – tunL) responsible for tunicamycin biosynthesis in the producing organisms Streptomyces chartreusis and S. clavuligerus. Amongst these is a putative radical SAM enzyme (TunB) with a potentially unique role in biosynthetic carbon-carbon bond formation, and an unusual glycosyltransferase involved in the formation of the anomeric-to-anomeric a,ß-1,11-glycosidic bond. Hence, a seven-step novel pathway is proposed for tunicamycin biosynthesis which may be useful for the design of new tunicamycin analogs with selective/enhanced translocase specificity.