Discovery of UDP-Glycosyltransferases and BAHD-Acyltransferases in the Biosynthesis of the Anti-Diabetic Plant Metabolite Montbretin A

Open Access Sandra Irmisch, Seohyun Jo, Christopher R Roach, Sharon Jancsik, Macaire M.S. Yuen, Lina Madilao, Mark Mark O'Neil-Johnson, Russell Williams, Stephen G Withers, Joerg Bohlmann Published July 2018. DOI: https://doi.org/10.1105/tpc.18.00406 ArticleFigures & DataInfo & Metrics PDF © 2018 American Society of Plant Biologists. All rights reserved. Abstract Plant specialized metabolism serves as a rich resource of biologically active molecules for drug discovery. The acylated flavonol glycoside montbretin A (MbA) and its precursor mini-MbA are potent inhibitors of human pancreatic α-amylase and are being developed as drug candidates for the treatment of type-2 diabetes. MbA occurs in corms of the ornamental plant montbretia (Crocosmia x crocosmiiflora), but a system or process to obtain large quantities of MbA is not currently available. Improved MbA production thus requires knowledge of its biosynthesis from the flavonol myricetin. Metabolite profiling and enzyme assays showed MbA formation and accumulation occurs during early stages of corm development. We established myricetin 3-O-rhamnoside (MR), myricetin 3-O-glucosyl rhamnoside (MRG) and myricetin 3-O-(6'-O-caffeoyl)-glucosyl rhamnoside (mini-MbA) as the first three intermediates during MbA biosynthesis. Contrasting transcriptomes of young and old corms revealed a set of differentially expressed UDP-sugar-dependent glycosyltransferases (UGTs) and BAHD-acyltransferases (BAHD-ATs). cDNA cloning and enzyme characterization identified UGT77B2 and UGT709G2 as the enzymes that catalyze the consecutive glycosylation of myricetin to produce MR and of MR to give MRG, respectively. We identified two BAHD-ATs, CcAT1 and CcAT2 that catalyze the acylation of MRG to complete the formation of mini-MbA. Received May 29, 2018. Accepted June 27, 2018.