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 -