Next to plants, bacteria account for most of the biomass on Earth. They are found everywhere, although certain species thrive only in specific ecological niches. These microorganisms biosynthesize a plethora of both primary and secondary metabolites, defined, respectively, as those required for the growth and maintenance of cellular functions and those not required for survival but offering a selective advantage for the producer under certain conditions. As a result, bacterial fermentation has long been used to manufacture valuable natural products of nutritional, agrochemical and pharmaceutical interest. The interactions of secondary metabolites with their biological targets have been optimized by millions of years of evolution and they are, thus, considered to be privileged chemical structures, not only for drug discovery. During the last two decades, functional genomics has allowed for an in-depth understanding of the underlying biosynthetic logic of secondary metabolites. This has, in turn, paved the way for the unprecedented use of bacteria as programmable biochemical workhorses. In this Review, we discuss the multifaceted use of bacteria as biological factories in diverse applications and highlight recent advances in targeted genetic engineering of bacteria for the production of valuable bioactive compounds. Emphasis is on current advances to access nature’s abundance of natural products.

除了植物，细菌占地球上大部分的生物量。它们随处可见，尽管某些物种仅在特定的生态位中繁衍生息。这些微生物生物合成大量初级和次级代谢物，分别定义为细胞功能生长和维持所需的代谢物，以及生存不需要但在某些条件下为生产者提供选择性优势的代谢物。因此，长期以来，细菌发酵一直被用于制造具有营养、农用化学和药物价值的有价值的天然产品。次级代谢物与其生物靶标的相互作用已通过数百万年的进化得到优化，因此，它们被认为是特殊的化学结构，不仅用于药物发现。在过去的二十年中，功能基因组学使人们能够深入了解次生代谢物的潜在生物合成逻辑。这反过来又为前所未有地使用细菌作为可编程的生化主力铺平了道路。在这篇综述中，我们讨论了细菌作为生物工厂在不同应用中的多方面用途，并强调了用于生产有价值的生物活性化合物的细菌靶向基因工程的最新进展。重点是当前在获取大自然丰富的天然产品方面取得的进展。我们讨论了细菌在不同应用中作为生物工厂的多方面用途，并强调了细菌靶向基因工程在生产有价值的生物活性化合物方面的最新进展。重点是当前在获取大自然丰富的天然产品方面取得的进展。我们讨论了细菌在不同应用中作为生物工厂的多方面用途，并强调了细菌靶向基因工程在生产有价值的生物活性化合物方面的最新进展。重点是当前在获取大自然丰富的天然产品方面取得的进展。