The <i>ldhA</i> Gene Encoding Fermentative <span style="font-variant: small-caps">l</span>-Lactate Dehydrogenase in <i>Corynebacterium Glutamicum</i> Is Positively Regulated by the Global Regulator GlxR
Bacterial metabolism shifts from aerobic respiration to fermentation at the transition from exponential to stationary growth phases in response to limited oxygen availability. <i>Corynebacterium glutamicum</i>, a Gram-positive, facultative aerobic bacterium used for industrial amino acid...
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MDPI AG
2021-03-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/3/550 |
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| author | Koichi Toyoda Masayuki Inui |
| author_facet | Koichi Toyoda Masayuki Inui |
| author_sort | Koichi Toyoda |
| collection | DOAJ |
| description | Bacterial metabolism shifts from aerobic respiration to fermentation at the transition from exponential to stationary growth phases in response to limited oxygen availability. <i>Corynebacterium glutamicum</i>, a Gram-positive, facultative aerobic bacterium used for industrial amino acid production, excretes <span style="font-variant: small-caps;">l</span>-lactate, acetate, and succinate as fermentation products. The <i>ldhA</i> gene encoding <span style="font-variant: small-caps;">l</span>-lactate dehydrogenase is solely responsible for <span style="font-variant: small-caps;">l</span>-lactate production. Its expression is repressed at the exponential phase and prominently induced at the transition phase. <i>ldhA</i> is transcriptionally repressed by the sugar-phosphate-responsive regulator SugR and <span style="font-variant: small-caps;">l</span>-lactate-responsive regulator LldR. Although <i>ldhA</i> expression is derepressed even at the exponential phase in the <i>sugR</i> and <i>lldR</i> double deletion mutant, a further increase in its expression is still observed at the stationary phase, implicating the action of additional transcription regulators. In this study, involvement of the cAMP receptor protein-type global regulator GlxR in the regulation of <i>ldhA</i> expression was investigated. The GlxR-binding site found in the <i>ldhA</i> promoter was modified to inhibit or enhance binding of GlxR. The <i>ldhA</i> promoter activity and expression of <i>ldhA</i> were altered in proportion to the binding affinity of GlxR. Similarly, <span style="font-variant: small-caps;">l</span>-lactate production was also affected by the binding site modification. Thus, GlxR was demonstrated to act as a transcriptional activator of <i>ldhA</i>. |
| first_indexed | 2024-03-09T05:10:29Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-09T05:10:29Z |
| publishDate | 2021-03-01 |
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| series | Microorganisms |
| spelling | doaj.art-dfe48abe8f904320ac997d3e182025612023-12-03T12:50:21ZengMDPI AGMicroorganisms2076-26072021-03-019355010.3390/microorganisms9030550The <i>ldhA</i> Gene Encoding Fermentative <span style="font-variant: small-caps">l</span>-Lactate Dehydrogenase in <i>Corynebacterium Glutamicum</i> Is Positively Regulated by the Global Regulator GlxRKoichi Toyoda0Masayuki Inui1Research Institute of Innovative Technology for the Earth (RITE), 9-2 Kizugawadai, Kizugawa, Kyoto 619-0292, JapanResearch Institute of Innovative Technology for the Earth (RITE), 9-2 Kizugawadai, Kizugawa, Kyoto 619-0292, JapanBacterial metabolism shifts from aerobic respiration to fermentation at the transition from exponential to stationary growth phases in response to limited oxygen availability. <i>Corynebacterium glutamicum</i>, a Gram-positive, facultative aerobic bacterium used for industrial amino acid production, excretes <span style="font-variant: small-caps;">l</span>-lactate, acetate, and succinate as fermentation products. The <i>ldhA</i> gene encoding <span style="font-variant: small-caps;">l</span>-lactate dehydrogenase is solely responsible for <span style="font-variant: small-caps;">l</span>-lactate production. Its expression is repressed at the exponential phase and prominently induced at the transition phase. <i>ldhA</i> is transcriptionally repressed by the sugar-phosphate-responsive regulator SugR and <span style="font-variant: small-caps;">l</span>-lactate-responsive regulator LldR. Although <i>ldhA</i> expression is derepressed even at the exponential phase in the <i>sugR</i> and <i>lldR</i> double deletion mutant, a further increase in its expression is still observed at the stationary phase, implicating the action of additional transcription regulators. In this study, involvement of the cAMP receptor protein-type global regulator GlxR in the regulation of <i>ldhA</i> expression was investigated. The GlxR-binding site found in the <i>ldhA</i> promoter was modified to inhibit or enhance binding of GlxR. The <i>ldhA</i> promoter activity and expression of <i>ldhA</i> were altered in proportion to the binding affinity of GlxR. Similarly, <span style="font-variant: small-caps;">l</span>-lactate production was also affected by the binding site modification. Thus, GlxR was demonstrated to act as a transcriptional activator of <i>ldhA</i>.https://www.mdpi.com/2076-2607/9/3/550corynebacterium glutamicumlactate dehydrogenaseGlxRtranscriptional regulation |
| spellingShingle | Koichi Toyoda Masayuki Inui The <i>ldhA</i> Gene Encoding Fermentative <span style="font-variant: small-caps">l</span>-Lactate Dehydrogenase in <i>Corynebacterium Glutamicum</i> Is Positively Regulated by the Global Regulator GlxR Microorganisms corynebacterium glutamicum lactate dehydrogenase GlxR transcriptional regulation |
| title | The <i>ldhA</i> Gene Encoding Fermentative <span style="font-variant: small-caps">l</span>-Lactate Dehydrogenase in <i>Corynebacterium Glutamicum</i> Is Positively Regulated by the Global Regulator GlxR |
| title_full | The <i>ldhA</i> Gene Encoding Fermentative <span style="font-variant: small-caps">l</span>-Lactate Dehydrogenase in <i>Corynebacterium Glutamicum</i> Is Positively Regulated by the Global Regulator GlxR |
| title_fullStr | The <i>ldhA</i> Gene Encoding Fermentative <span style="font-variant: small-caps">l</span>-Lactate Dehydrogenase in <i>Corynebacterium Glutamicum</i> Is Positively Regulated by the Global Regulator GlxR |
| title_full_unstemmed | The <i>ldhA</i> Gene Encoding Fermentative <span style="font-variant: small-caps">l</span>-Lactate Dehydrogenase in <i>Corynebacterium Glutamicum</i> Is Positively Regulated by the Global Regulator GlxR |
| title_short | The <i>ldhA</i> Gene Encoding Fermentative <span style="font-variant: small-caps">l</span>-Lactate Dehydrogenase in <i>Corynebacterium Glutamicum</i> Is Positively Regulated by the Global Regulator GlxR |
| title_sort | i ldha i gene encoding fermentative span style font variant small caps l span lactate dehydrogenase in i corynebacterium glutamicum i is positively regulated by the global regulator glxr |
| topic | corynebacterium glutamicum lactate dehydrogenase GlxR transcriptional regulation |
| url | https://www.mdpi.com/2076-2607/9/3/550 |
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