RESUMO
Bacillus subtilis is a Gram-positive bacterium that has gained an unprecedented reputation as an expression system at the industrial scale due to characteristics, such as GRAS (Generally recognized as safe), ease of genetic manipulation, high growth rate on the cheap substrate, and short fermentation cycle. This expression system has been widely accepted for the production of various chemicals, pharmaceutical products, food products, proteins, and enzymes. However, there are various hurdles to optimizing the production of heterologous protein in this expression system due to a lack of understanding regarding metabolic pathways and expression elements. In this review, we have emphasized strategies that can enhance the expression level of heterologous proteins in B. subtilis. These strategies include optimization of B. Subtilis strain, expression elements, such as promotors, UTR (Untranslated region), RBS (Ribosome binding site), signal peptide, and metabolic pathways. Finally, contemporary challenges and future perspectives of B. subtilis as an industrial-scale expression system are discussed.