Chemoenzymatic Synthesis of Glycosylated Macrolactam Analogues of the Macrolide Antibiotic YC-17
- 주제(키워드) antibacterial activity , glycosyltransferase , macrolide glycosides , Streptomyces venezuelae , YC-17
- 등재 SCIE, SCOPUS
- 발행기관 Wiley-VCH Verlag
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000119150
- 본문언어 영어
- Published As http://dx.doi.org/10.1002/adsc.201500250
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
YC-17 is a 12-membered ring macrolide antibiotic produced from Streptomyces venezuelae ATCC 15439 and is composed of the polyketide macrolactone 10-deoxymethynolide appended with D-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 S. venezuelae 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 in vitro. The enhanced therapeutic potential demonstrated by these glycosylated macrolactam analogues reveals the unique potential of chemoenzymatic synthesis in antibiotic drug discovery and development. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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