植物天然农药除虫菊酯的生物合成和应用研究进展

Biosynthesis and application of pyrethrins:a natural pesticide from plants

利用生物底盘进行生物农药的绿色低耗能生产是合成生物学未来发展的重要方向。除虫菊酯是一种源自菊科植物除虫菊的天然高效杀虫剂,具有广谱和强力的杀虫和驱虫作用,相较于化学合成的类似物(拟除虫菊酯),对哺乳动物毒性小,无环境危害,是生物农药的最优选择之一,具有广阔的应用前景。天然除虫菊酯含有六种主要成分,由两种异型萜类酸配体和茉莉酸合成途径来源的三种醇配体缩合而成。本文总结了除虫菊酯的研究历程,重点介绍了其生物合成途径解析与生物制造等方面的进展,综述了近期解析的细胞色素P450等相关生物合成酶,并讨论除虫菊酯生产中涉及的调控、转运和底盘适配等尚待解决的问题。随着合成生物学技术的发展,利用已解析的代谢合成途径在微生物等底盘表达体系规模化生产除虫菊酯,能够为合成生物学生产绿色生物农药的科学理论与应用实践提供重要范例。

How to produce safe pesticides in chassis through energy-saving and environmentally friendly methods is one of challenges for synthetic biology.As a natural botanical insecticide,Pyrethrins derived from Pyrethrum(Tanacetum cinerariifolium)have good insecticidal and deworming activities with broad spectrum.Compared with chemical synthetic counterparts(pyrethroids),pyrethrins are less toxic and harmful to environment and human.These characteristics make pyrethrins not only one of the most ideal biological pesticides so far with broad applications and great potentials,but also candidates for their production via synthetic biology in the future.In this article,we review the discovery and chemical and biological characteristics of pyrethrins as well as the elucidation of their biosynthetic pathway by summarizing the catalytic enzymes identified recently including cytochrome P450s,dehydrogenases,methyltransferase and phosphatase etc.The synthesis process is mainly involved three parts:the synthesis of acid moieties,the synthesis of alcohol moieties and the condensation of acids and alcohols to esters.At present,the synthesis of acid moieties has been largely deciphered,and genes encoding key enzymes for acid-alcohol condensation have also been determined,but the synthesis of alcohol moieties needs to be explored further.With the identification of a large number of gene elements and the function of related genes in the plants,the rise of synthetic biology and the progress of synthetic technology,it is possible to express heterologous genes in chassis,integrate the pathway of heterologous synthesis to produce targeted products.This also makes it possible to express the metabolic pathway for the production of pyrethrins and their derivatives in suitable microbial chassis.Therefore,this review also focuses on challenges that need to be addressed in this regard,including regulation,transportation and chassis adaptation for more efficient production,and forecasts future development.We hope that more research progress could provide a solid scientific basis and application guidance for the biosynthesis of the green and effective pesticide,and finally realize the large-scale production of pyrethrins.