Ecofriendly Synthesis of L-Carnosine in Metabolically Engineered Corynebacterium glutamicum by Reinforcing Precursor Accumulation
- Authors
- Kim, Minhye; Ko, Young Jin; Jeong, Da Woon; Jeong, Wu-Young; Han, Sung Ok
- Issue Date
- 18-6월-2021
- Publisher
- AMER CHEMICAL SOC
- Keywords
- L-carnosine; L-histidine; biobased synthesis; pentose phosphate pathway; antioxidant; Corynebacterium glutamicum
- Citation
- ACS SYNTHETIC BIOLOGY, v.10, no.6, pp.1553 - 1562
- Indexed
- SCIE
SCOPUS
- Journal Title
- ACS SYNTHETIC BIOLOGY
- Volume
- 10
- Number
- 6
- Start Page
- 1553
- End Page
- 1562
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/127837
- DOI
- 10.1021/acssynbio.1c00168
- ISSN
- 2161-5063
- 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 beta-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.
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