鲁比斯科
功能(生物学)
酶
突变体
计算生物学
生物化学
定向进化
生物
蛋白质工程
突变
化学
遗传学
基因
作者
Noam Prywes,Naiya R. Phillips,Luke M. Oltrogge,Sebastian Lindner,Leah J. Taylor‐Kearney,Yi-Chin Candace Tsai,Benoit de Pins,Aidan E. Cowan,Hana A. Chang,Renée Z. Wang,L Hall,Daniel Bellieny‐Rabelo,Hunter Nisonoff,Rachel F. Weissman,Avi I. Flamholz,David Ding,Abhishek Bhatt,Oliver Mueller‐Cajar,Patrick M. Shih,Ron Milo
出处
期刊:Nature
[Nature Portfolio]
日期:2025-01-22
被引量:1
标识
DOI:10.1038/s41586-024-08455-0
摘要
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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