AUTHOR=Peng Yu , Huan Yi , Chen Jing-Jing , Chen Tian-Jiao , Lei Lei , Yang Jin-Ling , Shen Zhu-Fang , Gong Ting , Zhu Ping 

TITLE=Microbial biotransformation to obtain stilbene methylglucoside with GPR119 agonistic activity

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1148513

DOI=10.3389/fmicb.2023.1148513

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>Limitation of pharmaceutical application of resveratrol (RSV) and piceatannol (PIC) continue to exist, there is a need to obtain the superior analogs of two stilbenes with promoted activity, stability, and bioavailability. Microbial transformation has been suggested as a common and efficient strategy to solve the above problems.</p></sec><sec><title>Methods</title><p>In this study, <italic>Beauveria bassiana</italic> was selected to transform RSV and PIC. LC-MS and NMR spectroscopies were used to analyze the transformed products and identify their structures. The biological activities of these metabolites were evaluated <italic>in vitro</italic> with GPR119 agonist and insulin secretion assays. Single factor tests were employed to optimize the biotransformation condition.</p></sec><sec><title>Results</title><p>Three new methylglucosylated derivatives of PIC (<bold>1</bold>–<bold>3</bold>) and two known RSV methylglucosides (<bold>4</bold> and <bold>5</bold>) were isolated and characterized from the fermentation broth. Among them, <bold>1</bold> not only showed moderate GPR119 agonistic activity with 65.9%, but also promoted insulin secretion level significantly (12.94 ng/mg protein/hour) at 1 μM. After optimization of fermentation conditions, the yield of <bold>1</bold> reached 45.53%, which was increased by 4.2-fold compared with the control.</p></sec><sec><title>Discussion</title><p>Our work presents that 3-<italic>O</italic>-MG PIC (<bold>1</bold>), obtained by microbial transformation, is an effective and safer ligand targeting GPR119, which lays a foundation for the anti-diabetic drug design in the future.</p></sec>