Machine learning-guided acyl-ACP reductase engineering for improved in vivo fatty alcohol production

Jonathan C. Greenhalgh, Sarah A. Fahlberg, Brian F. Pfleger, Philip A. Romero

Nature Communications 2021 article cited by 96

importance 5/10 solved Microbial Metabolic Engineering and Bioproduction industrial biotech stage: research

Fatty acyl reductase enzymes were a bottleneck to high-flux microbial production of fatty alcohols, limiting bioproduction yields.

Fatty alcohols are industrial chemicals; better enzymes could enable sustainable microbial manufacturing of them.

A machine learning-driven approach iteratively searched the protein fitness landscape over ten design-test-learn rounds to engineer improved FAR enzymes.

Engineered enzymes produced over twofold more fatty alcohols than starting natural sequences; top sequence showed enhanced catalytic rate on palmitoyl-ACP.

Peer-reviewed Nature Communications paper with 96 citations reporting a twofold production improvement via ML-guided engineering.

Venue Nature Communications
Published 2021
Work type article
Authors Jonathan C. Greenhalgh, Sarah A. Fahlberg, Brian F. Pfleger, Philip A. Romero
Citations 96 (OpenAlex, at import time)
References 49
Model or method not stated in source
Organization not stated in source
Primary source https://doi.org/10.1038/s41467-021-25831-w
Open access gold
Keywords machine learning, enzyme engineering, fatty alcohols, protein fitness landscape, metabolic engineering
5 / 10

real but narrower advance

Removing enzyme bottleneck for microbial fatty alcohol production, an industrial chemical; twofold yield gain stated but market/problem scale not quantified.

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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