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.

Milbemycins 是一组 16 元大环内酯，具有出色的杀螨、杀虫和驱虫活性，可由多种链霉菌属物种产生。由于对哺乳动物的毒性低，米尔倍霉素及其衍生物被广泛应用于农业、医疗和兽医行业。丙城链霉菌，一种产生米尔倍霉素的菌株，在过去的几十年里已经被测序和深入研究。在这篇小型综述中，我们全面回顾了在阐明米尔倍霉素细胞生产的生物合成途径和调控网络的研究工作中取得的进展。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倍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，菌株改良和新型米尔倍霉素衍生物的产生将极大地受益于未来使能技术的发展以及对米尔倍霉素生物合成基础及其生产调控的更深入理解。S.bingchengensis。该小型综述还提出，未来通过基因组最小化、系统代谢工程和合成生物学方法可以大大提高米尔倍霉素的过量生产。