Function of l-Pipecolic acid as a compatible solute in Corynebacterium glutamicum as the basis for its production under hyperosmolar conditions

Pipecolic acid or L-PA is a cyclic amino acid derived from L-lysine which has gained interest in the recent years within the pharmaceutical and chemical industries. L-PA can be produced efficiently using recombinant Corynebacterium glutamicum strains by expanding the natural L-lysine biosynthetic pathway. We show that de novo synthesized or externally added L-PA partially is beneficial for growth under hyper-osmotic stress conditions. C. glutamicum cells accumulated L-PA under elevated osmotic pressure and released it after an osmotic down shock. The proline permease ProP was identified as a candidate L-PA uptake system since RNAseq analysis revealed increased proP RNA levels upon L-PA production mRNA profiles of a C. glutamicum pipecolic acid producer compared with the mRNA profiles of a C. glutamicum proline producer. Samples were generated in triplicated and pooled