Engineered jadomycin analogues with altered sugar moieties revealing JadS as a substrate flexible O-glycosyltransferase
| Autor: | Xifen Zhu, Liyuan Li, Jinwei Ren, Mingxin Shi, Carlos Olano, Guohui Pan, Guomin Ai, Wubin Gao, Keqiang Fan, Keqian Yang, José A. Salas |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Glycosylation
Stereochemistry 010402 general chemistry 01 natural sciences Applied Microbiology and Biotechnology Substrate Specificity chemistry.chemical_compound Biosynthesis Bacterial Proteins Glycosyltransferase Combinatorial Chemistry Techniques Sugar moiety Sugar biology 010405 organic chemistry Substrate (chemistry) Glycosyltransferases General Medicine Isoquinolines Streptomyces 0104 chemical sciences Biosynthetic Pathways chemistry Polyketides biology.protein Jadomycin B Sugars Biotechnology |
| Zdroj: | Applied microbiology and biotechnology. 101(13) |
| ISSN: | 1432-0614 |
| Popis: | Glycosyltransferases (GTs)-mediated glycodiversification studies have drawn significant attention recently, with the goal of generating bioactive compounds with improved pharmacological properties by diversifying the appended sugars. The key to achieving glycodiversification is to identify natural and/or engineered flexible GTs capable of acting upon a broad range of substrates. Here, we report the use of a combinatorial biosynthetic approach to probe the substrate flexibility of JadS, the GT in jadomycin biosynthesis, towards different non-native NDP-sugar substrates, enabling us to identify six jadomycin B analogues with different sugar moieties. Further structural engineering by precursor-directed biosynthesis allowed us to obtain 11 new jadomycin analogues. Our results for the first time show that JadS is a flexible O-GT that can utilize both L- and D- sugars as donor substrates, and tolerate structural changes at the C2, C4 and C6 positions of the sugar moiety. JadS may be further exploited to generate novel glycosylated jadomycin molecules in future glycodiversification studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|