Dataset Information

Systems metabolic engineering of Corynebacterium glutamicum for the bioproduction of biliverdin via protoporphyrin independent pathway.

ABSTRACT:

Background

Biliverdin, a prospective recyclable antioxidant and one of the most important precursors for optogenetics, has received growing attention. Biliverdin is currently produced by oxidation of bilirubin from mammalian bile using chemicals. However, unsustainable procedures of extraction, chemical oxidation, and isomer separation have prompted bio-based production using a microbial cell factory.

Results

In vitro thermodynamic analysis was performed to show potential candidates of bottleneck enzymes in the pathway to produce biliverdin. Among the candidates, hemA and hemL were overexpressed in Corynebacterium glutamicum to produce heme, precursor of biliverdin. To increase precursor supply, we suggested a novel hemQ-mediated coproporphyrin dependent pathway rather than noted hemN-mediated protoporphyrin dependent pathway in C. glutamicum. After securing precursors, hmuO was overexpressed to pull the carbon flow to produce biliverdin. Through modular optimization using gene rearrangements of hemA, hemL, hemQ, and hmuO, engineered C. glutamicum BV004 produced 11.38?±?0.47?mg/L of biliverdin at flask scale. Fed-batch fermentations performed in 5?L bioreactor with minimal medium using glucose as a sole carbon source resulted in the accumulation of 68.74 ± 4.97?mg/L of biliverdin, the highest titer to date to the best of our knowledge.

Conclusions

We developed an eco-friendly microbial cell factory to produce biliverdin using C. glutamicum as a biosystem. Moreover, we suggested that C. glutamicum has the thermodynamically favorable coproporphyrin dependent pathway. This study indicated that C. glutamicum can work as a powerful platform to produce biliverdin as well as heme-related products based on the rational design with in vitro thermodynamic analysis.

SUBMITTER: Seok J

PROVIDER: S-EPMC6441180 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Systems metabolic engineering of <i>Corynebacterium glutamicum</i> for the bioproduction of biliverdin via protoporphyrin independent pathway.

Seok Jiho J Ko Young Jin YJ Lee Myeong-Eun ME Hyeon Jeong Eun JE Han Sung Ok SO

Journal of biological engineering 20190329

<h4>Background</h4>Biliverdin, a prospective recyclable antioxidant and one of the most important precursors for optogenetics, has received growing attention. Biliverdin is currently produced by oxidation of bilirubin from mammalian bile using chemicals. However, unsustainable procedures of extraction, chemical oxidation, and isomer separation have prompted bio-based production using a microbial cell factory.<h4>Results</h4>In vitro thermodynamic analysis was performed to show potential candidat ...[more]

PMID: 30976317

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