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A map of the rubisco biochemical landscape

2025/01/22 by Noam Prywes, Naiya R. Phillips, Luke M. Oltrogge +18 · 1 voice · 66 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Biochemistry #Biology #Chemistry #Computational biology #Directed evolution #Enzyme #Function (biology) #Gene #Genetics #Microbial Metabolic Engineering and Bioproduction #Mutant #Mutation #Photosynthetic Processes and Mechanisms #Plant biochemistry and biosynthesis #Protein engineering #RuBisCO

paper · pdf · doi:10.1038/s41586-024-08455-0

published in Nature 638(8051), 823-828 (Nature Portfolio)

openalex publication_date 2025/01/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

Abstract Rubisco is the primary CO 2 -fixing enzyme of the biosphere 1 , yet it has slow kinetics 2 . The roles of evolution and chemical mechanism in constraining its biochemical function remain debated 3,4 . Engineering efforts aimed at adjusting the biochemical parameters of rubisco have largely failed 5 , although recent results indicate that the functional potential of rubisco has a wider scope than previously known 6 . Here we developed a massively parallel assay, using an engineered Escherichia coli 7 in which enzyme activity is coupled to growth, to systematically map the sequence–function landscape of rubisco. Composite assay of more than 99% of single-amino acid mutants versus CO 2 concentration enabled inference of enzyme velocity and apparent CO 2 affinity parameters for thousands of substitutions. This approach identified many highly conserved positions that tolerate mutation and rare mutations that improve CO 2 affinity. These data indicate that non-trivial biochemical changes are readily accessible and that the functional distance between rubiscos from diverse organisms can be traversed, laying the groundwork for further enzyme engineering efforts.

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