In recent years, due to the extreme shortage of fossil resources around the world, microorganisms have been extensively studied as cell factories to meet people's demand for materials such as chemicals and fuels. The expression ‘cell factory’ first appeared in the 1970s, and due to the development of biotechnology and engineering, the concept of cell factory was gradually proposed and widely used in the 1990s(Nikel and Mattanovich, 2021). Microbial cell factory, on the other hand, refers to the use of microorganisms as production hosts in biotechnology to achieve the industrialization of target products and obtain renewable and cheap raw materials(Liu et al., 2013). However, because of the complexity of the microbial cell network, model bacteria are often used as chassis microorganisms, including Escherichia coli(Guo et al., 2020; Kim et al., 2023), Saccharomyces cerevisiae(Guo et al., 2023b; Meng et al., 2020), and Bacillus sp.(Jeong et al., 2022; Luo et al., 2022). Because of its wide variety and clear genetic background, Bacillus sp. is a popular candidate for microbial cell factories.

Bacillus sp. is a type of bacteria that produces spores. Mainly exists in soil, water, air, animal intestines, and other places, to the outside harmful substances, have strong resistance(Neef et al., 2021). It can use cheap carbon sources as substrate, effectively secrete extracellular proteins, and show a relatively stable state in the fermentation process. At the same time, the relatively clear genetic background, mature gene manipulation tools, and metabolic pathway regulation methods of Bacillus sp. are more attractive for researchers to study(Luo et al., 2022). More importantly, it is non-pathogenic, does not contain external toxins and endotoxins, and can secrete a variety of antimicrobial peptides, so that it has a long history of safe use in the food industry. For example, subtilin secreted by Bacillus subtilis can be used as a food preservative in dairy products. Therefore, Bacillus sp. is considered to be a food-safe genus, which can be used in the production of industrial enzyme preparations, food additives and green pesticides(Halimi et al., 2010).

The characteristics of Bacillus sp. make its cell factory have the advantages of fast growth rate, strong metabolic capacity, relatively simple culture conditions, and large-scale production. At present, Bacillus . cell factories have been widely used in biomedicine, industrial enzymes, biofuels and other fields. By optimizing the expression system and culture conditions of the Bacillus sp. cell factory, efficient and economical production can be achieved, providing a powerful tool and platform for the development of the bioengineering field.

To better understand and demonstrate the development of Bacillus sp., this paper reviews the research progress of synthetic biology of Bacillus sp., including advances in genetic information, gene editing tools, regulation and expression tools, as well as various engineering research strategies and practical applications. Finally, we discussed the limitations of Bacillus sp. as a microbial cell factory and proposed possible solutions, which provided effective guidance for the construction of a Bacillus sp. microbial cell factory.