P90: Involvement of L-lactate-responsive transcriptional regulator LldR in controlling of expression of the ldhA gene encoding L-lactate dehydrogenase in Corynebacterium glutamicum

Corynebacterium glutamicum is a Gram-positive soil bacterium widely used in the industrial production of amino acids. It also produces lactate, succinate, and acetate under oxygen limitation, conditions which induce NAD⁺-dependent, ldhA-encoded L-lactate dehydrogenase that couples reduction of pyruvate to L-lactate with regeneration of NAD⁺, thereby maintaining cellular redox balance. As the redox balance is important not only for biosynthesis of cellular components but also for biotechnological productivity, ldhA expression should be tightly regulated. To clarify the ldhA regulatory mechanism, we used a strain chromosomally expressing an ldhA promoter-lacZ fusion and transposon mutagenesis. We revealed that ldhA itself was required for upregulation of ldhA. Given that deletion of the lldR gene encoding the transcriptional regulator LldR which binds to the ldhA promoter restored ldhA promoter activity in an ldhA mutant, LldR irreversibly represses ldhA expression in the ldhA mutant due to the mutant’s inability to produce LldR-inactivating L-lactate. Besides LldR, SugR, a global repressor of genes involved in sugar utilization, represses ldhA expression in the absence of sugar. Taken together, ldhA expression is controlled by SugR and LldR in response to the availability of sugar and the presence of L-lactate produced by LdhA, respectively.

This work was partially supported by a grant from the New Energy and Industrial Technology Development Organization (NEDO).