Chirality Matters: Synthesis and Consumption of the D-Enantiomer of Lactic Acid by Synechocystis sp Strain PCC6803

Both enantiomers of lactic acid, L-lactic acid and D-lactic acid, can be produced in a sustainable way by a photosynthetic microbial cell factory and thus from CO2, sunlight, and water. Several properties of polylactic acid (a polyester of polymerized lactic acid) depend on the controlled blend of these two enantiomers. Recently, cyanobacterium Synechocystis sp. strain PCC6803 was genetically modified to allow formation of either of these two enantiomers. This report elaborates on the D-lactic acid production achieved by the introduction of a D-specific lactate dehydrogenase from the lactic acid bacterium Leuconostoc mesenteroides into Synechocystis. A typical batch culture of this recombinant strain initially shows lactic acid production, followed by a phase of lactic acid consumption, until production "outcompetes" consumption at later growth stages. We show that Synechocystis is able to use D-lactic acid, but not L-lactic acid, as a carbon source for growth. Deletion of the organism's putative D-lactate dehydrogenase (encoded by slr1556), however, does not eliminate this ability with respect to D-lactic acid consumption. In contrast, D-lactic acid consumption does depend on the presence of glycolate dehydrogenase GlcD1 (encoded by sll0404). Accordingly, this report highlights the need to match a product of interest of a cyanobacterial cell factory with the metabolic network present in the host used for its synthesis and emphasizes the need to understand the physiology of the production host in detail.