Ecosystem

Enzyme

Escherichia coli

Assimilation (phonology)

Biology

Gene

Catalysis

Philosophy

Chemistry

Ecology

Synthetic biology

Metabolic pathway

Serine

Glycine

Formate

Carbon flux

Linguistics

Computational biology

Amino acid

Biosynthesis

Biochemistry

ACS Synthetic Biology

Assimilation of one-carbon compounds presents a key biochemical challenge that limits their use as sustainable feedstocks for microbial growth and production. The reductive glycine pathway is a synthetic metabolic route that could provide an optimal way for the aerobic assimilation of reduced C1 compounds. Here, we show that a rational integration of native and foreign enzymes enables the tetrahydrofolate and glycine cleavage/synthase systems to operate in the reductive direction, such that Escherichia coli satisfies all of its glycine and serine requirements from the assimilation of formate and CO2. Importantly, the biosynthesis of serine from formate and CO2 does not lower the growth rate, indicating high flux that is able to provide 10% of cellular carbon. Our findings assert that the reductive glycine pathway could support highly efficient aerobic assimilation of C1-feedstocks.

In Vivo Assimilation of One-Carbon via a Synthetic Reductive Glycine Pathway in Escherichia coli