Bacillus subtilis has been studied for more than half a century, ever since the dawn of molecular biology, as a representative Gram-positive bacterium and cell factory. Two characteristic capacities of B. subtilis, namely its natural competence for DNA uptake and high-level enzyme secretion, have been investigated and exploited intensively during these long years. As a consequence, this bacterium has evolved into an excellent platform for synthetic biological research and development. In this review, we outline basic concepts for B. subtilis cell factory engineering, and we describe several examples of its applications in the production of proteins and high-value metabolites. In particular, we highlight engineering approaches that can make the already very efficient Bacillus protein secretion pathways even more efficient for the production of enzymes and pharmaceutical proteins. We further showcase examples of metabolic engineering in B. subtilis based on synthetic biology principles to produce various high-value or health-promoting substances, especially inositol stereoisomers. We conclude that the versatile traits of B. subtilis, combined with multi-omics approaches and rapidly developing technologies for genome engineering and high-throughput screening enable us to modify and optimize this bacterium’s metabolic circuits to deliver compounds that are needed for a green and sustainable society as well as a healthy population.

自从分子生物学问世以来，枯草芽孢杆菌作为代表性的革兰氏阳性细菌和细胞工厂已有超过半个世纪的研究历史。在这些漫长的岁月中，枯草芽孢杆菌的两个特征能力，即其天然的DNA吸收能力和高水平的酶分泌，已得到了广泛的研究和开发。结果，该细菌已发展成为合成生物学研究和开发的绝佳平台。在这篇综述中，我们概述了枯草芽孢杆菌细胞工厂工程的基本概念，并描述了其在蛋白质和高价值代谢产物生产中的几个应用实例。特别是，我们重点介绍了可以使本已非常高效的工程方法芽孢杆菌的蛋白质分泌途径对于生产酶和药用蛋白质更为有效。我们进一步展示了基于合成生物学原理在枯草芽孢杆菌中进行代谢工程的实例，以生产各种高价值或促进健康的物质，尤其是肌醇立体异构体。我们得出的结论是，枯草芽孢杆菌的多种性状，与多组学方法以及基因组工程和高通量筛选的快速发展技术相结合，使我们能够修改和优化该细菌的代谢途径，以提供绿色和可持续发展所需的化合物。社会以及健康的人口。