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Production of carbon-13-labeled cadaverine by engineered Corynebacterium glutamicum using carbon-13-labeled methanol as co-substrate

  • Applied genetics and molecular biotechnology
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Abstract

Methanol, a one-carbon compound, can be utilized by a variety of bacteria and other organisms as carbon and energy source and is regarded as a promising substrate for biotechnological production. In this study, a strain of non-methylotrophic Corynebacterium glutamicum, which was able to produce the polyamide building block cadaverine as non-native product, was engineered for co-utilization of methanol. Expression of the gene encoding NAD+-dependent methanol dehydrogenase (Mdh) from the natural methylotroph Bacillus methanolicus increased methanol oxidation. Deletion of the endogenous aldehyde dehydrogenase genes ald and fadH prevented methanol oxidation to carbon dioxide and formaldehyde detoxification via the linear formaldehyde dissimilation pathway. Heterologous expression of genes for the key enzymes hexulose-6-phosphate synthase and 6-phospho-3-hexuloisomerase of the ribulose monophosphate (RuMP) pathway in this strain restored growth in the presence of methanol or formaldehyde, which suggested efficient formaldehyde detoxification involving RuMP key enzymes. While growth with methanol as sole carbon source was not observed, the fate of 13C-methanol added as co-substrate to sugars was followed and the isotopologue distribution indicated incorporation into central metabolites and in vivo activity of the RuMP pathway. In addition, 13C-label from methanol was traced to the secreted product cadaverine. Thus, this synthetic biology approach led to a C. glutamicum strain that converted the non-natural carbon substrate methanol at least partially to the non-native product cadaverine.

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Ethical statement and acknowledgments

This work was supported by SynMet, a 09-EuroSYNBIO-FP-023 project, funded in part by DFG through grant WE 2320/2-1, and by EU-FP7 project PROMYSE “Products from Methanol by Synthetic Cell Factories.” This article does not contain any studies with human participants or animals performed by any of the authors. LL declares that he has no conflict of interest. JP declares that he has no conflict of interest. MC declares that he has no conflict of interest. SH declares that she has no conflict of interest. JCP declares that he has no conflict of interest. VFW declares that he has no conflict of interest. The authors gratefully acknowledge fruitful discussions with the groups of Julia Vorholt, Wim Quax, and Trygve Brautaset.

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  1. Genetics of Prokaryotes, Faculty of Biology and Center for Biotechnology, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany

    Lennart Leßmeier, Johannes Pfeifenschneider & Volker F. Wendisch

  2. LISBP-INSA de Toulouse, 135 avenue de Rangueil, 31077, Toulouse CEDEX 04, France

    Marc Carnicer, Stephanie Heux & Jean-Charles Portais

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  1. Lennart Leßmeier
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  2. Johannes Pfeifenschneider
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  3. Marc Carnicer
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  4. Stephanie Heux
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  5. Jean-Charles Portais
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  6. Volker F. Wendisch
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Correspondence to Volker F. Wendisch.

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Lennart Leßmeier and Johannes Pfeifenschneider contributed equally to this work.

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Leßmeier, L., Pfeifenschneider, J., Carnicer, M. et al. Production of carbon-13-labeled cadaverine by engineered Corynebacterium glutamicum using carbon-13-labeled methanol as co-substrate. Appl Microbiol Biotechnol 99, 10163–10176 (2015). https://doi.org/10.1007/s00253-015-6906-5

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  • DOI: https://doi.org/10.1007/s00253-015-6906-5

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