Details
| Original language | English |
|---|---|
| Pages (from-to) | 995-1006 |
| Number of pages | 12 |
| Journal | Advanced Synthesis and Catalysis |
| Volume | 359 |
| Issue number | 6 |
| Early online date | 16 Feb 2017 |
| Publication status | Published - 21 Mar 2017 |
Abstract
Glycosylated small molecules are often bioactive and obtained mainly via microbial biotransformation especially by fungi. However, no responsible glycosylation gene/enzyme has yet been uncovered in a filamentous fungus. We report here the first identification of a phenolic glycosyltransferase MhGT1 from Mucor hiemalis. The substrate promiscuity of the new phenolic O-glycosyltransferase was explored by using phenols from Traditional Chinese Medicinal herbs as substrates. MhGT1 exhibited robust capabilities for the regio- and stereospecific O-glycosylation of 72 structurally diverse drug-like scaffolds and sterols with uridine diphosphate (UDP) glucose as a sugar donor. Unprecedentedly, MhGT1 showed higher regiospecificities and activities for prenylated phenols than for their non-prenylated analogues. Computational modelling of MhGT1 uncovered a truncated N-terminal domain of the enzyme consisting of hydrophobic and charged amino acid residues which contributed to the broad substrate scope and regiospecificity towards prenylated compounds. Our findings expand the ways to obtain new glycosyltransferases and also effectively apply the enzymatic approach to obtain glycosylated compounds in drug discovery. (Figure presented.).
Keywords
- computational modelling, enzymatic catalysis, glycosyltransferases, Mucor hiemalis, substrate promiscuity
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Advanced Synthesis and Catalysis, Vol. 359, No. 6, 21.03.2017, p. 995-1006.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Regio- and Stereospecific O-Glycosylation of Phenolic Compounds Catalyzed by a Fungal Glycosyltransferase from Mucor hiemalis
AU - Feng, Jin
AU - Zhang, Peng
AU - Cui, Yinglu
AU - Li, Kai
AU - Qiao, Xue
AU - Zhang, Ying Tao
AU - Li, Shu Ming
AU - Cox, Russell J.
AU - Wu, Bian
AU - Ye, Min
AU - Yin, Wen Bing
N1 - Funding Information: This work was supported by National Key Research and Development Program (2016YFD0400105) and the National Natural Science Foundation of China (Grant No 81222054). W.B.Y. is a scholar of “the 100 Talents Project” of CAS.We thank Dr. Istvan Molnar (University of Arizona) for the critical reading and helpful discussions.
PY - 2017/3/21
Y1 - 2017/3/21
N2 - Glycosylated small molecules are often bioactive and obtained mainly via microbial biotransformation especially by fungi. However, no responsible glycosylation gene/enzyme has yet been uncovered in a filamentous fungus. We report here the first identification of a phenolic glycosyltransferase MhGT1 from Mucor hiemalis. The substrate promiscuity of the new phenolic O-glycosyltransferase was explored by using phenols from Traditional Chinese Medicinal herbs as substrates. MhGT1 exhibited robust capabilities for the regio- and stereospecific O-glycosylation of 72 structurally diverse drug-like scaffolds and sterols with uridine diphosphate (UDP) glucose as a sugar donor. Unprecedentedly, MhGT1 showed higher regiospecificities and activities for prenylated phenols than for their non-prenylated analogues. Computational modelling of MhGT1 uncovered a truncated N-terminal domain of the enzyme consisting of hydrophobic and charged amino acid residues which contributed to the broad substrate scope and regiospecificity towards prenylated compounds. Our findings expand the ways to obtain new glycosyltransferases and also effectively apply the enzymatic approach to obtain glycosylated compounds in drug discovery. (Figure presented.).
AB - Glycosylated small molecules are often bioactive and obtained mainly via microbial biotransformation especially by fungi. However, no responsible glycosylation gene/enzyme has yet been uncovered in a filamentous fungus. We report here the first identification of a phenolic glycosyltransferase MhGT1 from Mucor hiemalis. The substrate promiscuity of the new phenolic O-glycosyltransferase was explored by using phenols from Traditional Chinese Medicinal herbs as substrates. MhGT1 exhibited robust capabilities for the regio- and stereospecific O-glycosylation of 72 structurally diverse drug-like scaffolds and sterols with uridine diphosphate (UDP) glucose as a sugar donor. Unprecedentedly, MhGT1 showed higher regiospecificities and activities for prenylated phenols than for their non-prenylated analogues. Computational modelling of MhGT1 uncovered a truncated N-terminal domain of the enzyme consisting of hydrophobic and charged amino acid residues which contributed to the broad substrate scope and regiospecificity towards prenylated compounds. Our findings expand the ways to obtain new glycosyltransferases and also effectively apply the enzymatic approach to obtain glycosylated compounds in drug discovery. (Figure presented.).
KW - computational modelling
KW - enzymatic catalysis
KW - glycosyltransferases
KW - Mucor hiemalis
KW - substrate promiscuity
UR - http://www.scopus.com/inward/record.url?scp=85013448394&partnerID=8YFLogxK
U2 - 10.1002/adsc.201601317
DO - 10.1002/adsc.201601317
M3 - Article
AN - SCOPUS:85013448394
VL - 359
SP - 995
EP - 1006
JO - Advanced Synthesis and Catalysis
JF - Advanced Synthesis and Catalysis
SN - 1615-4150
IS - 6
ER -