Chemoenzymatic Synthesis of Glycosylated Macrolactam Analogues of the Macrolide Antibiotic YC‐17. Issue 12 (24th August 2015)

• Record Type: Journal Article
• Authors: Shinde, Pramod B.; Oh, Hong‐Se; Choi, Hyemin; Rathwell, Kris; Ban, Yeon Hee; Kim, Eun Ji; Yang, Inho; Lee, Dong Gun; Sherman, David H.; Kang, Han‐Young; Yoon, Yeo Joon
• Is Part Of: Advanced synthesis & catalysis. Volume 357:Issue 12(2015)
• Page Start: 2697
• Page End: 2711
• Publication Date: 2015-08-24
• Subjects: Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201500250
• Languages: English
• ISSNs: 1615-4150

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>YC‐17 is a 12‐membered ring macrolide antibiotic produced from <italic>Streptomyces venezuelae</italic> ATCC 15439 and is composed of the polyketide macrolactone 10‐deoxymethynolide appended with <sc>D</sc>‐desosamine. In order to develop structurally diverse macrolactam analogues of YC‐17 with improved therapeutic potential, a combined approach involving chemical synthesis and engineered cell‐based biotransformation was employed. Eight new antibacterial macrolactam analogues of YC‐17 were generated by supplying a novel chemically synthesized macrolactam aglycone to <italic>S. venezuelae</italic> mutants harboring plasmids capable of synthesizing several unnatural sugars for subsequent glycosylation. Some YC‐17 macrolactam analogues were active against erythromycin‐resistant bacterial pathogens and displayed improved metabolic stability <italic>in vitro</italic>. The enhanced therapeutic potential demonstrated by these glycosylated macrolactam analogues reveals the unique potential of chemoenzymatic synthesis in antibiotic drug discovery and development.</p> <p> <graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgj2fzmk1cp" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /> </p> </abstract>