Increased dipicolinic acid production with an enhanced <i>spoVF</i> operon in <i>Bacillus subtilis</i> and medium optimization

Dipicolinic acid (DPA) is a multi-functional agent for cosmetics, antimicrobial products, detergents, and functional polymers. The aim of this study was to design a new method for producing DPA from renewable material. The <i>Bacillus subtilis spoVF</i> operon encodes enzymes for DPA synthase and the part of lysine biosynthetic pathway. However, DPA is only synthesized in the sporulation phase, so the productivity of DPA is low level. Here, we report that DPA synthase was expressed in vegetative cells, and DPA was produced in the culture medium by replacement of the <i>spoVFA</i> promoter with other highly expressed promoter in <i>B. subtilis</i> vegetative cells, such as <i>spoVG</i> promoter. DPA levels were increased in the culture medium of genetically modified strains. DPA productivity was significantly improved up to 29.14 g/L in 72 h culture by improving the medium composition using a two-step optimization technique with the Taguchi methodology.