Comparative RNAseq analyses between P. acidipropionici WGS7 and P. acidipropionici ATCC 55737

Propionic acid (PA) is a three-carbon molecule commonly used as a food preservative and increasingly, as a precursor for the synthesis of monomers. Propionibacterium spp. are the best biological producers of PA. In fact, a recent report showed that if a yield of 0.6 g/g is achieved, biological production of PA would be economically competitive with petrochemical production. To achieve that yield, a library of Propionibacterium strains was used to generate a new strain that can achieve the commercially desirable yield from sucrose. The genome of the new strain was sequenced and a series of SNPs were found to be responsible for the improved phenotype. Using a combination of transcriptomics the relevant mutations were expounded. Differential RNA-sequencing between the wild-type and the mutant strain identified the relevant genomic changes responsible for the PA yield improvement. Notably, an increase in the specific consumption rate of sucrose was attributed to a SNP in the promoter region of a sugar transporter. Similarly, a mutation in a polar amino acid transporter improved acid tolerance, and an improvement in the electron transport system rewired the metabolism to yield an improved PA phenotype. These changes resulted in a lower acetic acid by-product generation and a higher PA yield. The productivity of the new strain was augmented with the design of a fed-batch process to achieve titres of 70 g/L through the use of a mathematically design fed-strategy. Overall design: Differential transcriptome expression was used to analyse changes leading to high propionic acid production.