Dissection of the Glycosylation in the Biosynthesis of the Heptadecaglycoside Antibiotic Saccharomicin A

Abstract

Oligosaccharide natural products have diverse biological activities and represent a potentially important source for drug development. In this study, we focus on the glycosylation pathway in the biosynthesis of saccharomicin A (SA-A), an oligosaccharide antibiotic containing 17 sugar moieties. By extensive gene-knockout studies with comparative metabolic profile analysis, we established a complete pathway in assembling the heptadecasaccharide chain of SA-A, the longest saccharide chain found in natural products.

Microbial Oligosaccharides with Biomedical Applications

“…The last two Eva residues are incorporated into M12 under the repeated actions of Sam12. Finally, authors hypothesize that sulfation of Fuc1 is predominantly completed after the assembly of the oligosaccharide chain, which is attributed to the existence of the sulfated Fuc (sFuc) in heptadecaglycoside [ 57 ].…”

Synthesis of the Branched Tetrasaccharide Fragment of Saccharomicin A

“…Saccharomicin A is a heptadecasaccharide isolated by Kong and co-workers that possesses broad spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens (Figure ). The continued global threat of antimicrobial resistance has created a pressing need for new antimicrobials, − and saccharomicin A or its analogue holds promise to help fill this role. Before saccharomicin can serve as a lead compound, however, it will be necessary to develop a route that is flexible enough for analogue production.…”

“…While the glycosyltransferases responsible for the installation of the sugars have been identified, the complete biosynthesis has yet to be elucidated. 3,4 As a consequence, the saccharomicins continue to attract attention from the synthetic community. 5−8 Our group has had an ongoing interest in the total synthesis of saccharomicins.…”

“…Before saccharomicin can serve as a lead compound, however, it will be necessary to develop a route that is flexible enough for analogue production. While the glycosyltransferases responsible for the installation of the sugars have been identified, the complete biosynthesis has yet to be elucidated. , As a consequence, the saccharomicins continue to attract attention from the synthetic community. − …”