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

Nico J. Claassens*, Ari Satanowski, Viswanada R. Bysani, Beau Dronsella, Enrico Orsi, Vittorio Rainaldi, Suzan Yilmaz, Sebastian Wenk, Steffen N. Lindner

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

5 Citations (Scopus)


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.

Original languageEnglish
Title of host publicationOne-Carbon Feedstocks for Sustainable Bioproduction
EditorsAn-Ping Zeng, Nico J. Claassens
Place of PublicationCham
ISBN (Electronic)9783031068546
ISBN (Print)9783031068539
Publication statusPublished - 2 Apr 2022

Publication series

NameAdvances in Biochemical Engineering/Biotechnology
ISSN (Print)0724-6145
ISSN (Electronic)1616-8542


  • Formate
  • Glycine cleavage/synthase system
  • Metabolic engineering
  • Methanol
  • One-carbon substrates
  • Reductive glycine pathway
  • Synthetic biology


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