doi: 10.1038/nchem.1351
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Biosynthesis of the tunicamycin antibiotics proceeds via unique exo-glycal intermediates

       
       
        Filip J. Wyszynski, Seung Seo Lee, Tomoaki Yabe, Hua Wang, Juan Pablo Gomez-Escribano, Mervyn J. Bibb,Soo Jae Lee, Gideon J. Davies & Benjamin G. Davis
       
        The tunicamycins are archetypal nucleoside antibiotics targeting bacterial peptidoglycan biosynthesis and eukaryotic protein N-glycosylation. Understanding the biosynthesis of their unusual carbon framework may lead to variants with improved selectivity. Here, we demonstrate in vitro recapitulation of key sugar-manipulating enzymes from this pathway. TunA is found to exhibit unusual regioselectivity in the reduction of a key α,β-unsaturated ketone. The product of this reaction is shown to be the preferred substrate for TunF--an epimerase that converts the glucose derivative to a galactose. In Streptomyces strains in which another gene (tunB) is deleted, the biosynthesis is shown to stall at this exo-glycal product. These investigations confirm the combined TunA/F activity and delineate the ordering of events in the metabolic pathway. This is the first time these surprising exo-glycal intermediates have been seen in biology. They suggest that construction of the aminodialdose core of tunicamycin exploits their enol ether motif in a mode of C-C bond formation not previously observed in nature, to create an 11-carbon chain.
       
       
来源：生物谷