Integrating metabolic and evolutionary engineering for enhanced propionic acid production under cross stress: a multi-omics perspective

We performed a combination of metabolic engineering (deletion of ldh and poxB and overexpression of mmc) with evolutionary engineering (selection under oxygen stress, acid stress and osmotic stress) in Propionibacterium acidipropionici. The results indicated that the mutants had superior physiological activity, especially the mutant III obtained from P. acidipropionici-Δldh-ΔpoxB+mmc by evolutionary engineering, with 1.5-3.5 times higher growth rates, as well as a 37.1% increase of PA titer and a 37.8% increase PA productivity compared to the wild type. Moreover, the 5.5-fold upregulation of Dps, 2 to 4-fold upregulation of ABC-type glycine betaine transporter and 3-fold upregulation of SOD indicated that these genes were likely in key regulons for the adaptation to abiotic stresses. An approximately 2.5-fold upregulation of mmc was also found. The results showed the multidirectional variation tendency of P. acidipropionici under cross stress and provide in-depth insights into the mechanism of tolerance and high production of PA.