An emergent biosynthetic pathway to essential amino acids by metabolic metathesis

Rivollier, J.; Gosling, S.; Pezo, V.; Heck, M.-P.; MARLIERE, P.

doi:10.1101/2023.09.06.556532

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bioRxiv · 10.1101/2023.09.06.556532

An emergent biosynthetic pathway to essential amino acids by metabolic metathesis

Rivollier, J.·Gosling, S.·Pezo, V.·Heck, M.-P.·MARLIERE, P.

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Abstract

An experimental approach to implanting foreign chemical reactions into living cells is to select for the catalytic production of a vital building-block such as an amino acid. Alkene metathesis is unknown in extant biochemistry, but is emerging as a new type of reaction to be catalyzed by protein enzymes. Here we show how the alkenic amino acid vinylglycine can be generated in a biocompatible reaction from 5-allyloxy-2-amino-pent-3-enoate (APE) by ring-closing metathesis catalyzed by a standard Hoveyda-Grubbs catalyst. The vinylglycine produced in situ is then used as a precursor of isoleucine and methionine, thus allowing the growth of strains of Escherichia coli requiring these essential amino acids. The robust nutritional screen we have developed paves the way for the directed evolution of genetically encoded metathesis enzymes and the chemical elaboration of metathesis coenzymes.

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Rivollier, J., Gosling, S., Pezo, V., Heck, M.-P., MARLIERE, P.. 2023-09-07. An emergent biosynthetic pathway to essential amino acids by metabolic metathesis. https://doi.org/10.1101/2023.09.06.556532

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