Developing Bacillus subtilis as cell factory for the production of the natural biocontrol compound pulcherrimin

Pulcherrimin, a natural metabolite produced by Bacillus subtilis, demonstrates a range of biological activities, including its potential use as a natural antimicrobial, antioxidant, or coloring agent. PS832 was selected as the host cell from four B. subtilis strains. Transcriptome data revealed that the leucine pathway has minimal impact on pulcherrimin titer, whereas the enzymes encoded by the yvmC-cypX operon are essential for achieving high pulcherrimin production. Alleviating transcriptional repression of the yvmC-cypX operon led to an increase in pulcherrimin titer representing a 9.5-fold enhancement to 487 mg/l. The mutant BSP17 showed 65 % inhibition rate on a phytopathogen, revealing its potential as a biocontrol agent. Furthermore, optimizing iron concentration in the medium resulted in pulcherrimin titers of 610 mg/l in shake flasks and 811 mg/l in a 1.5-l bioreactor. It is the highest reported titer and sets the stage for further metabolic engineering to achieve industrial-scale production of pulcherrimin.