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Engineering the Reductive Glycine Pathway: A Promising Synthetic Metabolism Approach for C1-Assimilation

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One-Carbon Feedstocks for Sustainable Bioproduction

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 180))

Abstract

In recent years the reductive glycine pathway (rGlyP) has emerged as a promising pathway for the assimilation of formate and other sustainable C1-feedstocks for future biotechnology. It was originally proposed as an attractive “synthetic pathway” to support formatotrophic growth due to its high ATP efficiency, linear structure, and limited overlap with native pathways in most microbial hosts. Here, we present the current state of research on this pathway including breakthroughs on its engineering. Different variants of the rGlyP are discussed, including its core module for formate to glycine conversion, as well as varying modules for substrate conversion to formate, and glycine assimilation routes. Very recently, the rGlyP has been successfully implemented for synthetic formatotrophic growth, as well as for growth on methanol, in some bacterial hosts. We discuss the engineering strategies employed in these studies, including growth-coupled selection of functional pathway modules. We also compare the rGlyP to other natural and synthetic C1-assimilation pathways. Finally, we provide an outlook on open challenges and opportunities for the rGlyP, including its engineering into more biotechnological hosts, as well as the still-to-be realized production of value-added chemicals via this pathway. We expect that further research on the rGlyP will support the efficient use of sustainable C1-substrates in bioproduction.

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Acknowledgements

The authors are grateful to their mentor Arren Bar-Even. He was supposed to act as an editor and contribute a chapter for this book, which he could sadly not do anymore due to his unexpected, early demise in September 2020. He inspired us and many others to work on the reductive glycine pathway and the C1-bio-economy. In the spirit of Arren we want to further carry his brilliant ideas and work in this research area. NJC acknowledges support from the VENI grant awarded to him by the Dutch Science Organization (NWO) (VI.Veni.192.156). SY is supported by the NWO-Gravitation Project BaSyC (024.003.019). EO and BD are supported by the German Ministry of Education and Research (BMBF) grant Transformate (033RC023G­). AS, VB, VR, SW, and SL acknowledge funding by the Max Planck Society.

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The authors have no competing interest to declare.

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Authors and Affiliations

  1. Laboratory of Microbiology, Wageningen University and Research, Wageningen, The Netherlands

    Nico J. Claassens & Suzan Yilmaz

  2. Systems and Synthetic Metabolism Group, Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany

    Ari Satanowski, Viswanada R. Bysani, Beau Dronsella, Enrico Orsi, Vittorio Rainaldi, Sebastian Wenk & Steffen N. Lindner

  3. Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany

    Steffen N. Lindner

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  1. Nico J. Claassens
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Correspondence to Nico J. Claassens .

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  1. Institute for Bioprocess and Biosystems Engineering, Hamburg University of Technology, Hamburg, Germany

    An-Ping Zeng

  2. Laboratory of Microbiology, Wageningen University, WAGENINGEN, The Netherlands

    Nico J. Claassens

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Claassens, N.J. et al. (2022). Engineering the Reductive Glycine Pathway: A Promising Synthetic Metabolism Approach for C1-Assimilation. In: Zeng, AP., Claassens, N.J. (eds) One-Carbon Feedstocks for Sustainable Bioproduction. Advances in Biochemical Engineering/Biotechnology, vol 180. Springer, Cham. https://doi.org/10.1007/10_2021_181

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