Fermentative production of the unnatural amino acid l-2-aminobutyric acid based on metabolic engineering View Full Text


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Article Info

DATE

2019-12

AUTHORS

Jian-Miao Xu, Jian-Qiang Li, Bo Zhang, Zhi-Qiang Liu, Yu-Guo Zheng

ABSTRACT

BACKGROUND: L-2-aminobutyric acid (L-ABA) is an unnatural amino acid that is a key intermediate for the synthesis of several important pharmaceuticals. To make the biosynthesis of L-ABA environmental friendly and more suitable for the industrial-scale production. We expand the nature metabolic network of Escherichia coli using metabolic engineering approach for the production of L-ABA. RESULTS: In this study, Escherichia coli THR strain with a modified pathway for threonine-hyperproduction was engineered via deletion of the rhtA gene from the chromosome. To redirect carbon flux from 2-ketobutyrate (2-KB) to L-ABA, the ilvIH gene was deleted to block the L-isoleucine pathway. Furthermore, the ilvA gene from Escherichia coli W3110 and the leuDH gene from Thermoactinomyces intermedius were amplified and co-overexpressed. The promoter was altered to regulate the expression strength of ilvA* and leuDH. The final engineered strain E. coli THR ΔrhtAΔilvIH/Gap-ilvA*-Pbs-leuDH was able to produce 9.33 g/L of L-ABA with a yield of 0.19 g/L/h by fed-batch fermentation in a 5 L bioreactor. CONCLUSIONS: This novel metabolically tailored strain offers a promising approach to fulfill industrial requirements for production of L-ABA. More... »

PAGES

43

References to SciGraph publications

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  • Journal

    TITLE

    Microbial Cell Factories

    ISSUE

    1

    VOLUME

    18

    Author Affiliations

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12934-019-1095-z

    DOI

    http://dx.doi.org/10.1186/s12934-019-1095-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112462281

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30819198


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        "description": "BACKGROUND: L-2-aminobutyric acid (L-ABA) is an unnatural amino acid that is a key intermediate for the synthesis of several important pharmaceuticals. To make the biosynthesis of L-ABA environmental friendly and more suitable for the industrial-scale production. We expand the nature metabolic network of Escherichia coli using metabolic engineering approach for the production of L-ABA.\nRESULTS: In this study, Escherichia coli THR strain with a modified pathway for threonine-hyperproduction was engineered via deletion of the rhtA gene from the chromosome. To redirect carbon flux from 2-ketobutyrate (2-KB) to L-ABA, the ilvIH gene was deleted to block the L-isoleucine pathway. Furthermore, the ilvA gene from Escherichia coli W3110 and the leuDH gene from Thermoactinomyces intermedius were amplified and co-overexpressed. The promoter was altered to regulate the expression strength of ilvA* and leuDH. The final engineered strain E. coli THR \u0394rhtA\u0394ilvIH/Gap-ilvA*-Pbs-leuDH was able to produce 9.33\u00a0g/L of L-ABA with a yield of 0.19\u00a0g/L/h by fed-batch fermentation in a 5\u00a0L bioreactor.\nCONCLUSIONS: This novel metabolically tailored strain offers a promising approach to fulfill industrial requirements for production of L-ABA.", 
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