The cryptic secondary metabolite biosynthetic gene clusters (BGCs) far outnumber currently known secondary metabolites. Heterologous production of secondary metabolite BGCs in suitable chassis facilitates yield improvement and discovery of new-to-nature compounds. The two juxtaposed conventional model microorganisms, Escherichia coli, Saccharomyces cerevisiae, have been harnessed as microbial chassis to produce a bounty of secondary metabolites with the help of certain host engineering. In last decade, engineering non-model microbes to efficiently biosynthesize secondary metabolites has received increasing attention due to their peculiar advantages in metabolic networks and/or biosynthesis. The state-of-the-art synthetic biology tools lead the way in operating genetic manipulation in non-model microorganisms for phenotypic optimization or yields improvement of desired secondary metabolites. In this review, we firstly discuss the pros and cons of several model and non-model microbial chassis, as well as the importance of developing broader non-model microorganisms as alternative programmable heterologous hosts to satisfy the desperate needs of biosynthesis study and industrial production. Then we highlight the lately advances in the synthetic biology tools and engineering strategies for optimization of non-model microbial chassis, in particular, the successful applications for efficient heterologous production of multifarious complex secondary metabolites, e.g., polyketides, nonribosomal peptides, as well as ribosomally synthesized and post-translationally modified peptides. Lastly, emphasis is on the perspectives of chassis cells development to access the ideal cell factory in the artificial intelligence-driven genome era.

神秘的次级代谢物生物合成基因簇（BGCs）远远超过目前已知的次级代谢物。在合适的底盘中异源生产次级代谢物 BGC 有助于提高产量和发现新的自然化合物。两种并列的常规模式微生物，大肠杆菌，酿酒酵母，已被用作微生物底盘，在某些宿主工程的帮助下产生大量的次生代谢物。在过去十年中，工程非模型微生物以有效地生物合成次级代谢物由于其在代谢网络和/或生物合成中的独特优势而受到越来越多的关注。最先进的合成生物学工具引领在非模型微生物中进行遗传操作，以优化表型或提高所需次级代谢物的产量。在这篇综述中，我们首先讨论了几种模式和非模式微生物底盘的优缺点，以及开发更广泛的非模式微生物作为替代可编程异源宿主以满足生物合成研究和工业生产的迫切需求的重要性。然后，我们重点介绍了用于优化非模型微生物底盘的合成生物学工具和工程策略的最新进展，特别是在高效异源生产多种复杂次级代谢物（例如聚酮化合物、非核糖体肽以及核糖体）方面的成功应用。合成和翻译后修饰的肽。最后，重点是底盘细胞开发的观点，以在人工智能驱动的基因组时代进入理想的细胞工厂。以及核糖体合成和翻译后修饰的肽。最后，重点是底盘细胞开发的观点，以在人工智能驱动的基因组时代进入理想的细胞工厂。以及核糖体合成和翻译后修饰的肽。最后，重点是底盘细胞开发的观点，以在人工智能驱动的基因组时代进入理想的细胞工厂。