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

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Pathway-specific enzymes from bamboo and crop leaves biosynthesize anti-nociceptive C-glycosylated flavones.
Communications Biology ( IF 5.2 ) Pub Date : 2020-03-06 , DOI: 10.1038/s42003-020-0834-3
Yuwei Sun ₁ , Zhuo Chen _{1,

2} , Jingya Yang ₃ , Ishmael Mutanda ₁ , Shiyi Li ₃ , Qian Zhang _{1,

2} , Ying Zhang _{1,

2} , Yulian Zhang _{1,

2} , Yong Wang ₁

Affiliation

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.

中文翻译：

竹和农作物叶片的途径特异性酶可生物合成抗伤害性C-糖基化黄酮。

C-糖基化黄酮（CGF）作为抗伤害感受性化合物很有希望。草科中的竹子和相关农作物的叶子是一种主要未被开发的生物资源，具有多种CGF。我们在这里报告了途径特异性酶，包括谷物作物和积累丰富CGF的竹类的C-糖基转移酶（CGT）和P450羟化酶。CGT的开采和修饰类黄酮骨架的P450的工程设计，使得在大肠杆菌细胞工厂中可以生产所需的CGF（产量为20-40 mg / L）。我们进一步探索了小鼠模型中主要CGF的抗伤害感受活性，并确定异Orientinin是最有效的，其神经镇痛和抗炎作用均优于罗丹定和阿司匹林等临床药物。

更新日期：2020-03-06

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