Abstract:Bacillus subtilis as a Gram-positive bacterium, which has clear genetic background and mature gene editing, and it was also considered as the important host of industrial enzymes. With the development of multi-omics sequencing technologies including transcriptome, proteome and metabolome, the rational design could simplify the Bacillus subtilis genome, reduce redundant regulatory and metabolic networks. It makes Bacillus subtilis more streamlined and easily to control. Furthermore, Bacillus subtilis as a heterologous enzyme expression host has been emerged the potential applications. This article briefly reviewed the advance in the effect Bacillus subtilis genome reduction, summarized the essential genes and the methods to identify them in Bacillus subtilis, highlighted the research progress and deletion strategies of Bacillus subtilis to enhance heterologous enzymes by deleting the genome, and demonstrated the important role of genome reduction in the construction of heterologous enzyme expression on the cellular chassis.