Construction of Corynebacterium glutamicum for synthesis of 5-aminolevulinic acid

  • LI Yuhong ,
  • LI Guirong ,
  • YANG Wenjun ,
  • MENG Yan ,
  • WANG Junzhe ,
  • ZHANG Chenglin
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  • (College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China)

Received date: 2022-03-07

  Revised date: 2022-03-23

  Online published: 2023-01-06

Abstract

As a value-added amino acid derivative, 5-aminolevulinic acid has been widely used in medicine, agriculture and husbandry due to the excellent activities. In this study, previously constructed C. glutamicum AL6 was used as an original strain to promote the productivity of 5-aminolevulinic acid. The isocitrate dehydrogenase-encoding gene icd was overexpressed to enhance the α-ketoglutarate and NADPH supply, the 5-aminolevulinic acid production by the resulting strain AL7 was increased by 18.3%; then a weak promoter PdapB was employed to downregulate the activity of α-oxoglutarate dehydrogenase complex. As a result, the α-oxoglutarate dehydrogenase complex activity was significantly decreased, and 1.92 g/L of 5-aminolevulinic acid was produced. However, accumulation of porphobilinogen and heme was observed. Dynamic regulation was applied to modulate the degradation of 5-aminolevulinic acid, which significantly decreased the concentration of porphobilinogen and heme. Meanwhile, the 5-aminolevulinic acid was significantly increased to 2.15 g/L. Finally, the effect of overexpressing exporter encoding gene on 5-aminolevulinic acid production was investigated. The efflux of 5-aminolevulinic acid by ThrE (an L-threonine exporter) of C. glutamicum was identified. Overexpression of rhtA resulted in much more improvement of 5-aminolevulinic acid than thrE. Furthermore, the effect of overexpressing rhtA by genome integration was better than by plasmid, and 2.69 g/L of 5-aminolevulinic acid was produced by the final strain AL12. This study could provide reference for improving synthesis of 5-aminolevulinic acid.

Cite this article

LI Yuhong , LI Guirong , YANG Wenjun , MENG Yan , WANG Junzhe , ZHANG Chenglin . Construction of Corynebacterium glutamicum for synthesis of 5-aminolevulinic acid[J]. Food and Fermentation Industries, 2022 , 48(24) : 8 -15 . DOI: 10.13995/j.cnki.11-1802/ts.031426

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