Increased flux through the TCA cycle enhances bacitracin production by Bacillus licheniformis DW2

The dodecapeptide antibiotic bacitracin, produced by several strains of Bacillus licheniformis and Bacillus subtilis, is widely used as an antibacterial animal feed additive. Several genetic strategies were explored to enhance its production. The availability of building block amino acids for bacitracin production was found to play an important role in its synthesis. In this study, the TCA cycle in the industrial strain B. licheniformis DW2 was strengthened by overexpression of the key enzymes citrate synthase and isocitrate dehydrogenase (ICDH). As the central metabolic pathway, the TCA cycle is a major source for energy supply and intermediates for anabolism. By enhancing flux through the TCA cycle, more energy and precursors were generated for amino acid biosynthesis and uptake, resulting in enlarged intracellular pool of bacitracin-containing amino acids for bacitracin production. This study unveiled the metabolic responses of the increased TCA cycle flux in B. licheniformis and provided a novel strategy for enhancing bacitracin production.