阿维菌素研究进展与产业综述

摘要：阿维菌素是阿维链霉菌发酵产生的十六元大环内酯类抗生素，主结构与米尔贝霉素相似，用于农业害虫防治和动物 的杀虫杀螨，还具有抗病毒、抗肿瘤、抗菌、消炎和醒酒等功效。它通过抑制RNA复制酶，阻止病毒蛋白进入细胞核以及封闭 剌突蛋白等方式，阻止病毒的复制感染和传播。已经产生抗药性的分枝杆菌和金黄色葡球菌也能被阿维菌素抑制。阿维菌素世 界上年需求量为5000吨左右，基本由中国企业生产。本文回顾了阿维菌素在菌种技术、发酵技术、提取技术、制剂技术发展和 组合生物学手段在本产业中的应用，建议通过菌种筛选技术、胞壁通透性调整、途径工程指导的基因改造、发酵过程的代谢流 控制、气升式发酵罐应用及细胞融合育种来提高发酵水平，将阿维链霉菌与米贝霉素链霉菌细胞融合育种。

Research advances and the industry of avermectin

Abstract Avermectin is a kind of 16-member macrolide antibiotics produced by Streptomyces avermectin fermentation, and is widely used in agricultural pest control, animal insecticidal, and acaricidal. Structurally, it is glycosylated milbemycin，and their genes of PKS (polyketide synthase) are highly homologous. Recent studies have found that avermectin also has anti-virus, anti-tumor, antibacterial, anti-inflammatory, sobriety, and other effects. Ivermectin (IVM) is effective against both Mycobacterium and Staphylococcus aureus strains. By means of inhibiting RNA helicase, preventing virus protein from entering nucleus, blocking virus spike protein, it can be used to deal with many kinds of viruses such as HIV, DENV, NDV, and so on. China is a major producer and exporter of avermectin, and the annual output is about 5000 tons. This paper reviews the development and technical progress of avermectin in China, discusses the toxicology, pharmacology, application, and industrial development of avermectin, summarizes the mechanism, application, and progress of various efficacy of avermectin, investigates the present situation of industry, and prospects the future development. It is suggested that improving the fermentation level by the method of strain screening technology, adjustment of cell wall permeability, genetic modification guided by pathway engineering, metabolic flow control in fermentation process, and application of airlift fermenter and so on. The protoplast fusion breeding of Streptomyces avermitilis and Streptomyces milbemycin strains may improve the strain level and produce new antibiotics.