Enhancing Carbon Metabolic Flow Ability for Titer Improvement of L‐Lactic Acid in <i>Bacillus coagulans</i> Through Heavy Ion Mutagenesis

Bacillus coagulans is a preferred producer for lactic acid, still facing the challenge of poor carbon metabolic flow ability. Here, an engineered B. coagulans strain P14 with improved carbon metabolic flow ability was developed for the first time through heavy ion mutagenesis combined with an enrichment strategy of acetic acid and sodium acetate, showing increased titer, productivity and yield of L-lactic acid compared to the parental strain. Notably, the activities of four enzymes involved in the glycolytic pathway of B. coagulans P14 were also higher. For batch fermentations, the engineered B. coagulans P14 strain showed improved production economy than the parental strain, which can produce 124.6 g/L L-lactic acid with a productivity of 7.1 g/L/h and a yield of 93% in a 5-L bioreactor under unsterile conditions, showing an increase of 6.0%, 24.3%, and 8.1% compared to the parental strain, respectively. This work showcases a method for rapidly breeding a robust lactic acid-producing strain through heavy ion mutagenesis combined with an enrichment strategy.