Transcriptional profiling reveals the effect of arginine on Actinobacillus succinogenes growth and fermentation.

Actinobacillus succinogenes is considered one of the most promising strains for succinic acid production due to its ability to utilize various carbon sources for high-concentration fermentation. However, limited understanding of genetic and metabolic changes during its growth and fermentation processes hinders further modification of A. succinogenes for application in SA production. In this study, we analyzed transcriptome profiles during A. succinogenes fermentation using high-throughput RNA sequencing. Compared to cells after 8 h of fermentation, cells at 34 h exhibited significant upregulation of genes related to glycerophospholipid metabolism and arginine biosynthesis pathways. We explored the effects of arginine on cell growth and fermentation by overexpressing or knocking down argH encoding argininosuccinate lyase (ArgH), a key enzyme in arginine biosynthesis. The integrity of the arginine metabolic pathway is essential for normal growth, and both exogenous addition of arginine and increased intracellular arginine metabolic flux improved cell growth and SA yield at low pH (5.0 ≤ pH ≤ 6.0). However, at non-low pH (6.0 ≤ pH ≤ 7.0), arginine had no significant effect on cell growth and SA yield. In a 3 L bioreactor under non-low pH conditions, the overexpression strain (::ArgH) produced 73.9 g/L SA with 1.65 g/L/h productivity, similar to the control strain. This implies that arginine metabolism in A. succinogenes is more associated with resistance to acid stress and less closely related to direct SA production. These findings provide insight into the critical physiological and biochemical processes of this non-model microorganism.