Genome-wide identification of the targets for genetic manipulation to improve l-lactate production by Saccharomyces cerevisiae by using a single-gene deletion strain collection

• Gene manipulation targets to improve l-lactate production by yeast were identified.
• For identification, a single-gene deletion strain collection was used.
• Deletion of the genes related to ribosome biogenesis improved l-lactate production.
• A single-gene deletion strain collection is useful to identify gene manipulation targets.

To identify genome-wide targets for gene manipulation for increasing l-lactate production in recombinant Saccharomyces cerevisiae strains, we transformed all available single-gene deletion strains of S. cerevisiae with a plasmid carrying the human l-lactate dehydrogenase gene, and examined l-lactate production in the obtained transformants. The thresholds of increased or decreased l-lactate production were determined based on l-lactate production by the standard strain in repetitive experiments. l-lactate production data for 4802 deletion strains were obtained, and deletion strains with increased or decreased l-lactate production were identified. Functional category analysis of genes whose deletion increased l-lactate production revealed that ribosome biogenesis-related genes were overrepresented. Most deletion strains for genes related to ribosome biogenesis exhibited increased l-lactate production in 200-ml batch cultures. We deleted the genes related to ribosome biogenesis in a recombinant strain of S. cerevisiae with a genetic background different from that of the above deletion strains, and examined the effect of target gene deletion on l-lactate production. We observed that deletion of genes related to ribosome biogenesis leads to increased l-lactate production by recombinant S. cerevisiae strains, and the single-gene deletion strain collection could be utilized in identifying target genes for improving l-lactate production in S. cerevisiae recombinant strains.