D-Lactate Metabolism in Lactic Acid Bacteria

Lactic acid bacteria (LAB) are a diverse group of Gram-positive microorganisms widely exploited for their capacity to ferment carbohydrates into lactic acid stereoisomers. Central to their metabolism is the production of D-lactate via D-lactate dehydrogenase (D-LDH), which catalyses the reduction of pyruvate to D-lactate while oxidising NADH to NAD+. This reaction not only maintains redox balance but also influences the optical purity and yield of fermentation products. Advances in structural biology have elucidated the active-site architecture of D-LDH and its allosteric regulation, while genetic and systems biology approaches have mapped the regulatory circuits governing d-ldh gene expression. Metabolic engineering of LAB strains has enabled enhanced D-lactate titres and enantiomeric excess, with applications spanning probiotic development, food preservation and the sustainable synthesis of polylactic acid. This overview integrates enzymatic, genetic and process-level insights into D-lactate metabolism in LAB.

Research from Nature Portfolio

Recent structural analyses have resolved high-resolution crystal structures of D-LDH enzymes from Lactobacillus delbrueckii, revealing conserved loop regions and active-site residues that underpin stereospecificity and thermostability. Concurrently, metabolic flux analysis combined with CRISPR interference in Lactococcus lactis has delineated the network of transcriptional regulators controlling d-ldh operons, identifying key nodes that modulate carbon flow under fermentative conditions. A further study engineered Streptococcus thermophilus to reroute pyruvate metabolism towards D-lactate production under acid stress, achieving enhanced yield and optical purity without compromising growth. Together, these investigations shed light on enzyme regulation and pathway control, offering new strategies for precision metabolic engineering of industrial LAB strains.

D-Lactate Metabolism in Lactic Acid Bacteria publication trend

The graph below shows the total number of articles in d-lactate metabolism in lactic acid bacteria across all publications each year (not limited to Nature Index journals).

Technical terms

D-lactate: The d-enantiomer of lactic acid produced by D-LDH, significant for its distinct physiological and material properties.

D-lactate dehydrogenase (D-LDH): An NAD-dependent enzyme that catalyses the reversible reduction of pyruvate to D-lactate.

Allosteric regulation: Control of enzyme activity through effector binding at sites remote from the active centre.

Metabolic flux analysis: Quantitative mapping of metabolite flows through cellular pathways to elucidate metabolic states.

Cofactor: A non-protein molecule, such as NADH, essential for enzymatic catalysis.

Optical purity: The proportion of a single enantiomer in a chiral compound, critical for polymerisation and biological function.

References

1. Diverse allosteric and catalytic functions of tetrameric d-lactate dehydrogenases from three Gram-negative bacteria. AMB Express (2014).
2. The D-Lactate Dehydrogenase from Sporolactobacillus inulinus Also Possessing Reversible Deamination Activity. PLOS ONE (2015).
3. Relative catalytic efficiencies and transcript levels of three d‐ and two l‐lactate dehydrogenases for optically pure d‐lactate production in Sporolactobacillus inulinus. MicrobiologyOpen (2018).