Ecofriendly Synthesis of l -Carnosine in Metabolically Engineered Corynebacterium glutamicum by Reinforcing Precursor Accumulation

Minhye Kim, Young Jin Ko, Da Woon Jeong, Wu Young Jeong, Sung Ok Han

Research output: Contribution to journalArticlepeer-review

Abstract

Biobased processes to minimize environmental pollutants have attracted much attention. l-Carnosine has been produced by chemical synthesis, and as an alternative to this method, we newly developed engineered Corynebacterium glutamicum synthesizing l-carnosine. To develop the strain, the pentose phosphate pathway (PPP) was enhanced by attenuating flux to nonoxidative PPP. Enhanced PPP strengthened the histidine pathway and produced 5.0 g/L l-histidine and 3.9 mg/L l-carnosine. Then, the histidine synthetic pathway was reinforced by overexpressing HisG and Rel. This pathway reduced feedback inhibition by l-histidine and strengthened the flux of the histidine pathway; thus, it produced 552.20 mg/g DCW l-histidine. As a result, enhancement of the PPP accumulates more l-histidine than the histidine pathway; thus, the PPP was further enhanced by pgi gene alteration. For sufficient β-alanine products, PanD was overexpressed and produced 99.17 mg/L l-carnosine. The final strain, Car15, which consolidated all three pathways, produced 323.26 mg/L l-carnosine via fed-batch fermentation. Finally, we confirmed the antioxidant and antiglycation effects of biologically synthesized l-carnosine, and the biologically synthesized l-carnosine showed inhibitory activity similar to that of commercial l-carnosine. Consequently, this study suggested a new biosynthetic process for l-carnosine and showed potential as a treatment for metabolic disorders through the assessment of its functions.

Original languageEnglish
JournalACS Synthetic Biology
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • antioxidant
  • biobased synthesis
  • Corynebacterium glutamicum
  • l -carnosine
  • l -histidine
  • pentose phosphate pathway

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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