Development of Bacillus subtilis cell factories for nutraceuticals production

Nutraceuticals are products that contribute to health maintenance or physiological regulation. With the continuous growth in market demand, increasing attention has been paid to their production methods. Chemical synthesis and extraction from plants or animals generally suffer from complex processes, high costs, low yields, raw material shortages, and environmental pollution. In contrast, microbial synthesis is emerging as a promising alternative route for nutraceutical production. Among various microbial hosts, Bacillus subtilis has become an often-considered ideal chassis cell for the biosynthesis of nutraceuticals due to its GRAS status, well-characterized genetic background, and mature genetic manipulation platforms. This review systematically summarizes the synthetic biology tools and advanced metabolic engineering strategies employed in the construction of B. subtilis cell factories, critically compares their limitations, and highlights their applications in the biosynthesis of nutraceuticals. Furthermore, current challenges and future research directions are discussed. In summary, B. subtilis is expected to play an increasingly critical role in the efficient and sustainable biosynthesis of nutraceuticals.