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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    28 Citations (Scopus)

    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

    Bibliographical note

    Publisher Copyright:
    © 2018, The Author(s).

    ASJC Scopus subject areas

    • General

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