Combining mechanistic and machine learning models for predictive engineering and optimization of tryptophan metabolism

Jie Zhang, Søren D. Petersen, Tijana Radivojević, Andrés Ramirez, Andrés Pérez-Manríquez, Eduardo Abeliuk, Benjamín J. Sánchez, Zak Costello et al.

Nature Communications 2020 article cited by 282

importance 5/10 partially solved Microbial Metabolic Engineering and Bioproduction metabolic engineering stage: research

Predicting which genetic designs improve yeast tryptophan production is difficult, making metabolic engineering slow and inefficient.

Engineering aromatic amino acid metabolism in living systems is a central goal of industrial metabolic engineering.

A genome-scale mechanistic model pinpointed engineering targets, and machine learning algorithms trained on biosensor-screened library data recommended pathway designs.

Best ML-guided designs improved tryptophan titer by up to 74% and productivity by up to 43% versus best training designs, from a single data-generation cycle.

Shows one ML-guided design cycle can yield large percentage gains in yeast tryptophan production.

Venue Nature Communications
Published 2020
Work type article
Authors Jie Zhang, Søren D. Petersen, Tijana Radivojević, Andrés Ramirez, Andrés Pérez-Manríquez, Eduardo Abeliuk, Benjamín J. Sánchez, Zak Costello et al.
Citations 282 (OpenAlex, at import time)
References 82
Model or method not stated in source
Organization not stated in source
Primary source https://doi.org/10.1038/s41467-020-17910-1
Open access gold
Keywords machine learning, metabolic engineering, tryptophan, yeast, genome-scale model
5 / 10

real but narrower advance

Abstract shows large tryptophan gains in yeast and frames the method as effectively directing metabolic engineering, but states no scale or end-use impact; industrial biotech importance is inferred.

Basis: inferred. Judged from the source text, which gives no explicit scale. Stated scale: not stated in source. Method and limits.

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