Authors
Dan Sun, Jie Wu, Ru-Li He, Jing Wu, Wei-Qiang Lin, He-Ping Zhao, Dong-Feng Liu, Wen-Wei Li
Published in
Metabolic engineering. Pages 102560. Oct 06, 2026. Epub Oct 06, 2026.
Abstract
Porphyrin-derived high-value chemicals are important for food, medicine, and fine chemicals manufacturing, yet the physiological complexity of tetrapyrrole metabolism constrains efficient bioproduction. Here, we systematically engineered the cytochrome-rich bacterium Shewanella oneidensis MR-1 for porphyrin production. A modular coproporphyrin III biosynthetic pathway was reconstructed and progressively optimized through hemB homolog selection, antioxidant defense engineering, attenuation of competing tetrapyrrole branches, genome-scale model-guided target mining, plasmid-backbone reassignment, and ribosome-binding site tuning. The resulting strain achieved a remarkable coproporphyrin III production of 1525.5 ± 37.3 mg·L-1 and was further raised to 1906.8 ± 39.2 mg·L-1 under 5-aminolevulinic acid supplementation condition. Integrated metabolomic analyses identified a riboflavin-associated redox response linked to improved production physiology, while extracellular product accumulation enabled efficient acetone-assisted crude recovery. The platform was further extended to protoporphyrin IX and heme production with titers of 612.7 ± 4.8 mg·L-1 and 107.4 ± 3.3 mg·L-1, respectively. This work demonstrates an integrated metabolic engineering strategy combining pathway reconstruction, physiological stress mitigation, model-guided target selection, and multilevel expression balancing for developing S. oneidensis as a porphyrin-producing cell factory.
PMID:
42838423
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.
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