Biosynthesis of organic photosensitizer Zn-porphyrin by diphtheria toxin repressor (DtxR)-mediated global upregulation of engineered heme biosynthesis pathway in Corynebacterium glutamicum

Young Jin Ko, Young Chul Joo, Jeong Eun Hyeon, Eunhye Lee, Myeong Eun Lee, Jiho Seok, Seung Wook Kim, Chulhwan Park, Sung Ok Han

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Abstract

Zn-porphyrin is a promising organic photosensitizer in various fields including solar cells, interface and biomedical research, but the biosynthesis study has been limited, probably due to the difficulty of understanding complex biosynthesis pathways. In this study, we developed a Corynebacterium glutamicum platform strain for the biosynthesis of Zn-coproporphyrin III (Zn-CP III), in which the heme biosynthesis pathway was efficiently upregulated. The pathway was activated and reinforced by strong promoter-induced expression of hemAM (encoding mutated glutamyl-tRNA reductase) and hemL (encoding glutamate-1-semialdehyde aminotransferase) genes. This engineered strain produced 33.54 ± 3.44 mg/l of Zn-CP III, while the control strain produced none. For efficient global regulation of the complex pathway, the dtxR gene encoding the transcriptional regulator diphtheria toxin repressor (DtxR) was first overexpressed in C. glutamicum with hemAM and hemL genes, and its combinatorial expression was improved by using effective genetic tools. This engineered strain biosynthesized 68.31 ± 2.15 mg/l of Zn-CP III. Finally, fed-batch fermentation allowed for the production of 132.09 mg/l of Zn-CP III. This titer represents the highest in bacterial production of Zn-CP III reported to date, to our knowledge. This study demonstrates that engineered C. glutamicum can be a robust biotechnological model for the production of photosensitizer Zn-porphyrin.

Original languageEnglish
Article number14460
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Corynebacterium glutamicum
Diphtheria Toxin
Photosensitizing Agents
Porphyrins
Heme
Up-Regulation
glutamate-1-semialdehyde 2,1-aminomutase
Genes
Fermentation
Biomedical Research
coproporphyrin III

ASJC Scopus subject areas

  • General

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Biosynthesis of organic photosensitizer Zn-porphyrin by diphtheria toxin repressor (DtxR)-mediated global upregulation of engineered heme biosynthesis pathway in Corynebacterium glutamicum. / Ko, Young Jin; Joo, Young Chul; Hyeon, Jeong Eun; Lee, Eunhye; Lee, Myeong Eun; Seok, Jiho; Kim, Seung Wook; Park, Chulhwan; Han, Sung Ok.

In: Scientific Reports, Vol. 8, No. 1, 14460, 01.12.2018.

Research output: Contribution to journalArticle

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