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Methylotrophy in the thermophilic Bacillus methanolicus, basic insights and application for commodity production from methanol

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Abstract

Using methanol as an alternative non-food feedstock for biotechnological production offers several advantages in line with a methanol-based bioeconomy. The Gram-positive, facultative methylotrophic and thermophilic bacterium Bacillus methanolicus is one of the few described microbial candidates with a potential for the conversion of methanol to value-added products. Its capabilities of producing and secreting the commercially important amino acids l-glutamate and l-lysine to high concentrations at 50 °C have been demonstrated and make B. methanolicus a promising target to develop cell factories for industrial-scale production processes. B. methanolicus uses the ribulose monophosphate cycle for methanol assimilation and represents the first example of plasmid-dependent methylotrophy. Recent genome sequencing of two physiologically different wild-type B. methanolicus strains, MGA3 and PB1, accompanied with transcriptome and proteome analyses has generated fundamental new insight into the metabolism of the species. In addition, multiple key enzymes representing methylotrophic and biosynthetic pathways have been biochemically characterized. All this, together with establishment of improved tools for gene expression, has opened opportunities for systems-level metabolic engineering of B. methanolicus. Here, we summarize the current status of its metabolism and biochemistry, available genetic tools, and its potential use in respect to overproduction of amino acids.

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Acknowledgments

Work related to methylotrophy in the authors’ laboratories is supported by FP7 project Promyse and the Swiss SystemsX.ch, Norwegian RCN and the German initiatives within the framework of the ERA-Net ERASysAPP.

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Authors and Affiliations

  1. Institute of Microbiology, ETH Zurich, Zurich, Switzerland

    Jonas E. N. Müller & Julia A. Vorholt

  2. Department of Molecular Biology, SINTEF Materials and Chemistry, Postboks 4760, Sluppen, 7465, Trondheim, Norway

    Tonje M. B. Heggeset & Trygve Brautaset

  3. Chair of Genetics of Prokaryotes, Faculty of Biology and CeBiTec, Bielefeld University, Bielefeld, Germany

    Volker F. Wendisch

  4. Department of Biotechnology, Norwegian University of Science and Technology, Trondheim, Norway

    Trygve Brautaset

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  1. Jonas E. N. Müller
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  2. Tonje M. B. Heggeset
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  3. Volker F. Wendisch
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  5. Trygve Brautaset
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Correspondence to Trygve Brautaset.

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Jonas E. N. Müller and Tonje M. B. Heggeset contributed equally to this work.

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Müller, J.E.N., Heggeset, T.M.B., Wendisch, V.F. et al. Methylotrophy in the thermophilic Bacillus methanolicus, basic insights and application for commodity production from methanol. Appl Microbiol Biotechnol 99, 535–551 (2015). https://doi.org/10.1007/s00253-014-6224-3

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