| Summary: | 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 <i>Bacillus</i> and <i>Clostridium</i> species, and its biosynthesis shares the first three reactions with the L-lysine pathway. <i>Corynebacterium glutamicum</i> 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 <i>C. glutamicum</i> to half-maximal at about 1.6 g·L<sup>−1</sup>. The first de novo production of DPA by <i>C. glutamicum</i> was established by overexpression of dipicolinate synthase genes from <i>Paenibacillus sonchi</i> genomovar <i>riograndensis</i> SBR5 in a <i>C. glutamicum</i> L-lysine producer strain. Upon systems metabolic engineering, DPA production to 2.5 g·L<sup>−1</sup> in shake-flask and 1.5 g·L<sup>−1</sup> 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 <i>P. stutzeri</i> enabled phosphite-dependent non-sterile DPA production.
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