Metabolic Engineering of for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic Acid.

Dipicolinic acid (DPA) is an aromatic dicarboxylic acid that mediates heat-stability and is easily biodegradable and non-toxic. Currently, the production of DPA is fossil-based, but bioproduction of DPA may help to replace fossil-based plastics as it can be used for the production of polyesters or polyamides. Moreover, it serves as a stabilizer for peroxides or organic materials. The antioxidative, antimicrobial and antifungal effects of DPA make it interesting for pharmaceutical applications. In nature, DPA is essential for sporulation of and species, and its biosynthesis shares the first three reactions with the L-lysine pathway. is a major host for the fermentative production of amino acids, including the million-ton per year production of L-lysine. This study revealed that DPA reduced the growth rate of to half-maximal at about 1.6 g·L. The first de novo production of DPA by was established by overexpression of dipicolinate synthase genes from genomovar SBR5 in a L-lysine producer strain. Upon systems metabolic engineering, DPA production to 2.5 g·L in shake-flask and 1.5 g·L in fed-batch bioreactor cultivations was shown. Moreover, DPA production from the alternative carbon substrates arabinose, xylose, glycerol, and starch was established. Finally, expression of the codon-harmonized phosphite dehydrogenase gene from enabled phosphite-dependent non-sterile DPA production.