Advances in genome-scale metabolic modeling of Bacillus subtilis

Bacillus subtilis is a key industrial microorganism widely used to produce enzymes, vitamins, antibiotics, and recombinant proteins. Its non-pathogenic nature, efficient protein secretion systems, and genetic tractability make it an ideal candidate for industrial biotechnology. Genome-scale metabolic modeling has emerged as a key systems biology approach to understand, explore and manipulate the metabolism of B. subtilis for improved strain performance. To date, the modeling efforts have resulted in fourteen published genome-scale metabolic reconstructions for B. subtilis; however, substantial opportunities for improvement remain, especially in integrating regulatory mechanisms for refining model accuracy. Furthermore, there is a growing trend toward modelling the cell as a whole system. This article is the first comprehensive and up-to-date review that highlights the genome sequencing, annotation efforts and the current state of genome-scale metabolic modeling for B. subtilis, emphasizing future directions.