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Production of 2,3-dihydroxyisovalerate by Enterobacter cloacae

Yang, Y; Zhang, Z; Lu, X; Gu, J; Wang, Y; Yao, Y; Liao, X; ... Hao, J; + view all (2020) Production of 2,3-dihydroxyisovalerate by Enterobacter cloacae. Enzyme and Microbial Technology , 140 , Article 109650. 10.1016/j.enzmictec.2020.109650. Green open access

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Abstract

2,3-Dihydroxyisovalerate is an intermediate of the valine synthesis pathway. However, neither natural microorganisms nor valine producing engineered strains have been reported yet to produce this chemical. Based on the 2,3-butanediol synthesis pathway, a biological route of 2,3-dihydroxyisovalerate production was developed using a budA and ilvD disrupted Klebsiella pneumoniae strain in our previous research. We hypothesised, that other 2,3-butanediol producing bacteria could be used for 2,3-dihydroxyisovalerate production. Here a budA disrupted Enterobacter cloacae was constructed, and this strain exhibited a high 2,3-dihydroxyisovalerate producing ability. Disruption of ilvD in E. cloacae ΔbudA further increased 2,3-dihydroxyisovalerate level. The disruption of budA, encoding an acetolactate decarboxylase, resulted in the acetolactate synthesized in the 2,3-butanediol synthesis pathway to flow into the valine synthesis pathway. The additional disruption of ilvD, encoding a dihydroxy acid dehydratase, prevented the 2,3-dihydroxyisovalerate to be further metabolized in the valine synthesis pathway. Thus, the disruption of both budA and ilvD in 2,3-butanediol producing strains might be an universal strategy for 2,3-dihydroxyisovalerate accumulation. After optimization of the medium components and culture parameters 31.2 g/L of 2,3-dihydroxyisovalerate was obtained with a productivity of 0.41 g/L h and a substrate conversion ratio of 0.56 mol/mol glucose in a fed-batch fermentation. This approach provides an economic way for 2,3-dihydroxyisovalerate production.

Type: Article
Title: Production of 2,3-dihydroxyisovalerate by Enterobacter cloacae
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.enzmictec.2020.109650
Publisher version: https://doi.org/10.1016/j.enzmictec.2020.109650
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Enterobacter cloacae; 2,3-dihydroxyisovalerate; 2,3-butanediol; branched-chain amino acid
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10109793
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