Construction of a synthetic metabolic pathway for the production of 2,4-dihydroxybutyric acid from homoserine
| العنوان: | Construction of a synthetic metabolic pathway for the production of 2,4-dihydroxybutyric acid from homoserine |
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| المؤلفون: | Clémentine Dressaire, Yoann Malbert, Jean Marie François, Florence Calvayrac, Thomas Walther, Hélène Cordier, Ceren Alkim |
| المساهمون: | Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Toulouse White Biotechnology (TWB), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Metabolic Engineering Metabolic Engineering, Elsevier, 2018, ⟨10.1016/j.ymben.2017.12.005⟩ Metabolic Engineering, . (2018) Metabolic Engineering, 2018, ⟨10.1016/j.ymben.2017.12.005⟩ |
| بيانات النشر: | HAL CCSD, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, homosérine, voie métabolique, Lactate dehydrogenase A, Homoserine, Bioengineering, Reductase, Applied Microbiology and Biotechnology, Metabolic engineering, 03 medical and health sciences, chemistry.chemical_compound, ingénierie métabolique, [CHIM.GENI]Chemical Sciences/Chemical engineering, Bacterial Proteins, Escherichia coli, Génie chimique, education, Butylene Glycols, chemistry.chemical_classification, education.field_of_study, biology, Lactococcus lactis, Chimical engineering, metabolic pathway, biology.organism_classification, Amino acid, Metabolic pathway, Butyrates, 030104 developmental biology, Enzyme, chemistry, Biochemistry, metabolic engineering, Biotechnology |
| الوصف: | 2,4-dihydroxybutyrate (DHB) is a precursor for the chemical synthesis of the methionine analogue 2-hydroxy-4-(methylthio)butyrate. Since no annotated metabolic pathway exists for its microbial production from sugar, we have conceived a two-step synthetic metabolic pathway which converts the natural amino acid homoserine to DHB. The pathway proceeds through the homoserine transaminase-catalyzed deamination of homoserine to obtain 2-oxo-4-hydroxybutyrate (OHB), and continues with the reduction of OHB to DHB, which is catalyzed by an OHB reductase enzyme. We identified homoserine transaminase and OHB reductase activity in several candidate enzymes which act on sterically cognate substrates, and improved OHB reductase activity of lactate dehydrogenase A of Lactococcus lactis by structure-based enzyme engineering. Fed-batch cultivation of a homoserine-overproducing Escherichia coli strain which expressed homoserine transaminase and OHB reductase enzymes resulted in the production of 5.3 g/L DHB at a yield of 0.1 g/g. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1096-7176 1096-7184 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a42dd1dda0dcc700edbfe7704bf81cc6 https://hal.archives-ouvertes.fr/hal-01886438/document |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a42dd1dda0dcc700edbfe7704bf81cc6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10967176 10967184 |
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