Metabolic Engineering of <i>Corynebacterium glutamicum</i> 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 p...
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MDPI AG
2022-03-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/4/730 |
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| author | Lynn S. Schwardmann Aron K. Dransfeld Thomas Schäffer Volker F. Wendisch |
| author_facet | Lynn S. Schwardmann Aron K. Dransfeld Thomas Schäffer Volker F. Wendisch |
| author_sort | Lynn S. Schwardmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T13:16:10Z |
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| language | English |
| last_indexed | 2024-03-09T13:16:10Z |
| publishDate | 2022-03-01 |
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| series | Microorganisms |
| spelling | doaj.art-1d439e4262364201959bd06459e26a952023-11-30T21:35:01ZengMDPI AGMicroorganisms2076-26072022-03-0110473010.3390/microorganisms10040730Metabolic Engineering of <i>Corynebacterium glutamicum</i> for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic AcidLynn S. Schwardmann0Aron K. Dransfeld1Thomas Schäffer2Volker F. Wendisch3Genetics of Prokaryotes, Faculty of Biology and CeBiTec, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, GermanyGenetics of Prokaryotes, Faculty of Biology and CeBiTec, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, GermanyMultiscale Bioengineering, Technical Faculty and CeBiTec, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, GermanyGenetics of Prokaryotes, Faculty of Biology and CeBiTec, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, GermanyDipicolinic 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.https://www.mdpi.com/2076-2607/10/4/730dipicolinic acid<i>Corynebacterium glutamicum</i>metabolic engineeringsustainable productionnonsterile fermentationphosphite |
| spellingShingle | Lynn S. Schwardmann Aron K. Dransfeld Thomas Schäffer Volker F. Wendisch Metabolic Engineering of <i>Corynebacterium glutamicum</i> for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic Acid Microorganisms dipicolinic acid <i>Corynebacterium glutamicum</i> metabolic engineering sustainable production nonsterile fermentation phosphite |
| title | Metabolic Engineering of <i>Corynebacterium glutamicum</i> for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic Acid |
| title_full | Metabolic Engineering of <i>Corynebacterium glutamicum</i> for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic Acid |
| title_fullStr | Metabolic Engineering of <i>Corynebacterium glutamicum</i> for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic Acid |
| title_full_unstemmed | Metabolic Engineering of <i>Corynebacterium glutamicum</i> for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic Acid |
| title_short | Metabolic Engineering of <i>Corynebacterium glutamicum</i> for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic Acid |
| title_sort | metabolic engineering of i corynebacterium glutamicum i for sustainable production of the aromatic dicarboxylic acid dipicolinic acid |
| topic | dipicolinic acid <i>Corynebacterium glutamicum</i> metabolic engineering sustainable production nonsterile fermentation phosphite |
| url | https://www.mdpi.com/2076-2607/10/4/730 |
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