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Integrated pathway mining and selection of an artificial CYP79-mediated bypass to improve benzylisoquinoline alkaloid biosynthesis

Microb Cell Fact. 2024-06; 
Musashi Takenaka, Kouhei Kamasaka, Kim Daryong, Keiko Tsuchikane, Seiha Miyazawa, Saeko Fujihana, Yoshimi Hori, Christopher J Vavricka, Akira Hosoyama, Hiroko Kawasaki, Tomokazu Shirai, Michihiro Araki, Akira Nakagawa, Hiromichi Minami, Akihiko Kondo, Tomohisa Hasunuma
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Gene Synthesis … All synthetic genes were optimized for E. coli codon usage, purchased from GenScript (NJ, USA) and cloned into pET23a (NdeI-BamHI sites). The optimized sequences are shown in Fig… Get A Quote

摘要

background: Computational mining of useful enzymes and biosynthesis pathways is a powerful strategy for metabolic engineering. Through systematic exploration of all conceivable combinations of enzyme reactions, including both known compounds and those inferred from the chemical structures of established reactions, we can uncover previously undiscovered enzymatic processes. The application of the novel alternative pathways enables us to improve microbial bioproduction by bypassing or reinforcing metabolic bottlenecks. Benzylisoquinoline alkaloids (BIAs) are a diverse group of plant-derived compounds with important pharmaceutical properties. BIA biosynthesis has developed into a prime example of metabolic enginee... More

关键词

3,4-dihydroxyphenylacetaldoxime, Artificial metabolic pathway, Benzylisoquinoline alkaloid production, Computational enzyme mining, Cytochrome P450, Tyrosine N-monooxygenase