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journal article Oct 21, 2014

Efficient hydroxyproline production from glucose in minimal media by Corynebacterium glutamicum

Francesco Falcioni Bruno Bühler ORCID Andreas Schmid ORCID
Biotechnology and Bioengineering Vol. 112 No. 2 pp. 322-330 · Wiley
View at Publisher Save 10.1002/bit.25442
Abstract
ABSTRACTThe efficient coupling of biotransformation steps to an existing fermentation pathway is an interesting strategy to expand the product portfolio of Corynebacterium glutamicum as whole‐cell biocatalyst. This is especially challenging if the biotransformation step comprises a direct link to central metabolism, as in the case of α‐ketoglutarate‐dependent oxygenase catalysis. Aiming at trans‐4‐hydroxy‐L‐proline (Hyp) production from glucose in a minimal medium, the proline‐4‐hydroxylase gene from Dactylosporangium sp. strain RH1 was introduced into a proline‐producing, isoleucine‐bradytroph C. glutamicum strain. The production of proline was found to be induced by isoleucine limitation. Proline and Hyp production were found to depend differently on isoleucine limitation. Severe isoleucine limitation was shown to result in proline accumulation and low hydroxylation rates both in batch and continuous cultivation set‐ups. The investigation of different steady states with various glucose/isoleucine molar ratios revealed that optimal conditions for Hyp production are met around a molar ratio of 46:1, where isoleucine limitation is sufficient to trigger proline production but the hydroxylation rate is high enough to convert the majority of formed proline to Hyp. A high cell‐density fed‐batch set‐up was designed, capable of producing 7.1 g L−1 of Hyp from glucose in 23 h with 98.5% conversion of proline to Hyp. Reaction engineering, specifically the fine‐tuning of the glucose/isoleucine concentration ratio, enabled control of the fermentation profile and thus the accumulation of the desired product Hyp from glucose in minimal and defined media. Biotechnol. Bioeng. 2015;112: 322–330. © 2014 Wiley Periodicals, Inc.
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Metrics
33
Citations
43
References
Details
Published
Oct 21, 2014
Vol/Issue
112(2)
Pages
322-330
License
View
Authors
F
Francesco Falcioni

Department of Biochemical and Chemical Engineering Laboratory of Chemical Biotechnology TU Dortmund University Emil‐Figge‐Strasse 66 Dortmund 44227 Germany

B
Bruno Bühler

Department of Biochemical and Chemical Engineering Laboratory of Chemical Biotechnology TU Dortmund University Emil‐Figge‐Strasse 66 Dortmund 44227 Germany

A
Andreas Schmid

Department of Biochemical and Chemical Engineering Laboratory of Chemical Biotechnology TU Dortmund University Emil‐Figge‐Strasse 66 Dortmund 44227 Germany

Funding
EU FP7 Award: 212281
Cite This Article
Francesco Falcioni, Bruno Bühler, Andreas Schmid (2014). Efficient hydroxyproline production from glucose in minimal media by Corynebacterium glutamicum. Biotechnology and Bioengineering, 112(2), 322-330. https://doi.org/10.1002/bit.25442
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