Pathway-specific enzymes from bamboo and crop leaves biosynthesize anti-nociceptive C-glycosylated flavones.

Communications Biology
Yuwei SunYong Wang

Abstract

C-glycosylated flavones (CGFs) are promising candidates as anti-nociceptive compounds. The leaves of bamboo and related crops in the grass family are a largely unexploited bioresource with a wide array of CGFs. We report here pathway-specific enzymes including C-glycosyltransferases (CGTs) and P450 hydroxylases from cereal crops and bamboo species accumulating abundant CGFs. Mining of CGTs and engineering of P450s that decorate the flavonoid skeleton allowed the production of desired CGFs (with yield of 20-40 mg/L) in an Escherichia coli cell factory. We further explored the antinociceptive activity of major CGFs in mice models and identified isoorientin as the most potent, with both neuroanalgesic and anti-inflammatory effects superior to clinical drugs such as rotundine and aspirin. Our discovery of the pain-alleviating flavonoids elicited from bamboo and crop leaves establishes this previously underutilized source, and sheds light on the pathway and pharmacological mechanisms of the compounds.

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Citations

Jul 14, 2020·Biochemical Society Transactions·Gregor Tegl, Bernd Nidetzky
Nov 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Zi-Long WangMin Ye
Jan 25, 2021·The Plant Journal : for Cell and Molecular Biology·Cheng-Yong FengLiang-Sheng Wang
Oct 26, 2021·The Plant Journal : for Cell and Molecular Biology·Xiaorong SunZhongbao Zhang

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Datasets Mentioned

BETA
AF155332.1

Methods Mentioned

BETA
glycosylation
dissection
MDA
enzymatic assay
electrophoresis
X-ray

Software Mentioned

TMHMM Server
MCScanx
Clustal Omega
Ensembl
Plant Compara
ImageJ
Mega X

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