1. Enzymatic Synthesis of Bioactive O-Glucuronides Using Plant Glucuronosyltransferases.
- Author
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Yue T, Chen R, Chen D, Liu J, Xie K, and Dai J
- Subjects
- Antirrhinum genetics, Biocatalysis, Enzyme Stability, Glucuronosyltransferase genetics, Glucuronosyltransferase metabolism, Kinetics, Molecular Structure, Perilla frutescens genetics, Plant Proteins genetics, Plant Proteins metabolism, Substrate Specificity, Antirrhinum enzymology, Glucuronides chemistry, Glucuronosyltransferase chemistry, Perilla frutescens enzymology, Plant Proteins chemistry
- Abstract
Many O-glucuronides exhibiting various pharmacological activities have been found in nature and in drug metabolism. The glucuronidation of bioactive natural products or drugs to generate glucuronides with better activity and druggability is important in drug discovery and research. In this study, by using two uridine diphosphate (UDP)-dependent glucuronosyltransferases (GATs, UGT88D4 and UGT88D7) from plants, we developed two glucuronidation approaches, pure enzyme catalysis in vitro and recombinant whole-cell catalysis in vivo, to efficiently synthesize bioactive O-glucuronides by the glucuronidation of natural products. In total, 14 O-glucuronides with different structures, including flavonoids, anthraquinones, coumarins, and lignans, were obtained, 7 of which were new compounds. Furthermore, one of the biosynthesized O-glucuronides, kaempferol-7- O-β-d-glucuronide (3a), potently inhibited protein tyrosine phosphatase (PTP) 1B with an IC
50 value of 8.02 × 10-6 M. Some of the biosynthesized O-glucuronides also exhibited significant antioxidant activities.- Published
- 2019
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