Back to Search
Start Over
Engineered jadomycin analogues with altered sugar moieties revealing JadS as a substrate flexible O-glycosyltransferase
- Source :
- Applied microbiology and biotechnology. 101(13)
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14320614
- Volume :
- 101
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Applied microbiology and biotechnology
- Accession number :
- edsair.doi.dedup.....8019d0cb398d26288ebb123f0bfde374