Deep learning-based k(cat) prediction enables improved enzyme-constrained model reconstruction

Li, Feiran,1993Chalmers tekniska högskola,Chalmers University of Technology (författare)

Enzyme turnover numbers (k(cat)) are key to understanding cellular metabolism, proteome allocation and physiological diversity, but experimentally measured k(cat) data are sparse and noisy. Here we provide a deep learning approach (DLKcat) for high-throughput k(cat) prediction for metabolic enzymes from any organism merely from substrate structures and protein sequences. DLKcat can capture k(cat) changes for mutated enzymes and identify amino acid residues with a strong impact on k(cat) values. We applied this approach to predict genome-scale k(cat) values for more than 300 yeast species. Additionally, we designed a Bayesian pipeline to parameterize enzyme-constrained genome-scale metabolic models from predicted k(cat) values. The resulting models outperformed the corresponding original enzyme-constrained genome-scale metabolic models from previous pipelines in predicting phenotypes and proteomes, and enabled us to explain phenotypic differences. DLKcat and the enzyme-constrained genome-scale metabolic model construction pipeline are valuable tools to uncover global trends of enzyme kinetics and physiological diversity, and to further elucidate cellular metabolism on a large scale.

Yuan, Le,1994Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)leyu (författare)
Lu, Hongzhong,1987Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)luho (författare)
Li, Gang,1991Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)gangl (författare)
Chen, Yu,1990Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)cheyu (författare)
Engqvist, Martin,1983Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)marengq (författare)
Kerkhoven, Eduard,1985Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)eduardk (författare)
Nielsen, Jens B,1962Chalmers tekniska högskola,Chalmers University of Technology,BioInnovation Institute (BII)(Swepub:cth)nielsenj (författare)
Chalmers tekniska högskolaBioInnovation Institute (BII) (creator_code:org_t)

Ingår i:Nature Catalysis: Springer Science and Business Media LLC5:8, s. 662-6722520-1158

Av författaren/redakt...: Li, Feiran, 1993; Yuan, Le, 1994; Lu, Hongzhong, 1 ...; Li, Gang, 1991; Chen, Yu, 1990; Engqvist, Martin ...; visa fler...; Kerkhoven, Eduar ...; Nielsen, Jens B, ...; visa färre...

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