Institute of Biopharmaceuticals, Taizhou University, 1139 Shifu Avenue, Jiaojiang District, Taizhou, 318000, Zhejiang, People's Republic of China.
Arch Microbiol. 2021 Dec;203(10):5849-5857. doi: 10.1007/s00203-021-02575-1. Epub 2021 Sep 22.
Milbemycins, a group of 16-membered macrocylic lactones with excellent acaricidal, insecticidal and anthelmintic activities, can be produced by several Streptomyces species. For the reason that they have low toxicity in mammals, milbemycins and their derivatives are widely used in agricultural, medical and veterinary industries. Streptomyces bingchenggensis, one of milbemycin-producing strains, has been sequenced and intensively investigated in the past decades. In this mini-review, we comprehensively revisit the progress that has been made in research efforts to elucidate the biosynthetic pathways and regulatory networks for the cellular production of milbemycins. The advances in the development of production strains for milbemycin and its derivatives are discussed along the strain-generation technical approaches of random mutagenesis, metabolic engineering and combinatorial biosynthesis. The research progress made so far indicates that strain improvement and generation of novel milbemycin derivatives will greatly benefit from future development of enabling technologies and deeper understanding of the fundamentals of biosynthesis of milbemycin and the regulation of its production in S. bingchenggensis. This mini-review also proposes that the overproduction of milbemycins could be greatly enhanced by genome minimization, systematical metabolic engineering and synthetic biology approaches in the future.
米尔贝霉素是一组具有优异杀虫、杀虫和驱虫活性的 16 元大环内酯类化合物，可由几种链霉菌产生。由于它们在哺乳动物中的毒性较低，米尔贝霉素及其衍生物在农业、医学和兽医行业中得到了广泛应用。米尔贝霉素产生菌之一的井冈链霉菌在过去几十年中已经被测序并进行了深入研究。在这篇迷你综述中，我们全面回顾了阐明米尔贝霉素细胞生物合成途径和调控网络的研究进展。沿着随机诱变、代谢工程和组合生物合成的菌株生成技术方法，讨论了米尔贝霉素及其衍生物生产菌株的开发进展。迄今为止的研究进展表明，未来通过赋予技术的发展和对米尔贝霉素生物合成基础以及其在井冈链霉菌中产生的调控的更深入理解，将极大地有利于菌株的改良和新型米尔贝霉素衍生物的产生。这篇迷你综述还提出，通过基因组最小化、系统代谢工程和合成生物学方法，未来可以大大提高米尔贝霉素的产量。
