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bioRxiv · 10.64898/2026.07.12.738062

Air-driven aldehyde synthesis in engineered bacteria via gene deletion and aryl-alcohol oxidase profiling

Dickey, R. M.·Bryan, J.·Somasundaram, V.·Anderson, S. R.·Phan, N.·Kunjapur, A. M.
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Abstract

Engineered bacterial routes for oxidation of non-native alcohols face three challenges: Nicotinamide-dependent enzymes are coupled to cellular redox metabolism, nicotinamide-independent aryl-alcohol oxidases (AAOs) usually express poorly in bacteria, and aldehyde products are rapidly modified by host enzymes. Here, we address these limitations by engineering aldehyde-retaining Escherichia coli for discovery and application of soluble bacterial AAOs. Screening 51 candidates revealed a high-expression sequence cluster containing enzymes that are active on diverse aromatic and furan-based alcohols. Pairing the top-performing AAO with designer pathways in aldehyde-retaining cells enabled modular C-N and C-C bond forming cascades starting from supplied alcohols. By making both the oxidase and its product compatible with the host, this work advances air-driven oxidation of diverse alcohols as a programmable entry point to aldehyde-derived chemistry in engineered bacteria.

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Dickey, R. M., Bryan, J., Somasundaram, V., Anderson, S. R., Phan, N., Kunjapur, A. M.. 2026-07-13. Air-driven aldehyde synthesis in engineered bacteria via gene deletion and aryl-alcohol oxidase profiling. https://doi.org/10.64898/2026.07.12.738062

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