# Monooxygenase-dehydrogenase cascade for sustained enzymatic remediation of TMA in salmon protein hydrolysates

**Authors:** Rasmus Ree, Øivind Larsen, Sushil Gaykawad, Sreerekha S. Ramanand, Antonio García-Moyano, Irina Elena Chiriac, Pål Puntervoll, Gro Elin Kjæreng Bjerga

PMC · DOI: 10.1128/aem.01242-25 · Applied and Environmental Microbiology · 2026-02-03

## TL;DR

Researchers developed an enzyme system to reduce the fishy odor in salmon protein hydrolysates by removing trimethylamine, making them more suitable for food and nutraceutical use.

## Contribution

A cost-effective dual enzyme cascade was developed to sustainably remove trimethylamine from fish protein hydrolysates.

## Key findings

- The mFMO/glucose dehydrogenase system reduced TMA by 75% in salmon protein hydrolysates.
- A trained sensory panel confirmed a significant improvement in odor after treatment.
- The system enables TMA removal with reduced cofactor costs, making it industrially viable.

## Abstract

Fish protein hydrolysates hold great promise as nutraceuticals, yet their application as food ingredients or nutraceuticals is currently limited by their fish-like odor. This odor is mainly due to the presence of trimethylamine (TMA), a volatile biogenic amine resulting from the breakdown of naturally occurring trimethylamine-N-oxide (TMAO) in marine fish. The bacterial trimethylamine monooxygenase mFMO can oxidize TMA into TMAO using molecular oxygen and the cofactor nicotinamide adenine dinucleotide phosphate (NADPH). We have established an enzyme cascade that takes advantage of glucose dehydrogenase to recycle NADPH from NADP+, significantly decreasing the cost of the reaction and paving the way for using the enzyme system in fish protein hydrolysates targeted for human consumption. We demonstrate that the dual enzyme system works in an industrially relevant substrate. Salmon protein hydrolysate treated with an mFMO/glucose dehydrogenase cocktail showed a 75% reduction in TMA. A trained sensory panel perceived an improved odor across several parameters, including a reduction in the characteristic TMA smell.

Marine by-products are a valuable source of high-quality peptide ingredients; however, their application in the food market is limited by the unpleasant fishy odor caused by trimethylamine (TMA). An enzyme that oxidizes TMA to the odor-free trimethylamine-N-oxide (TMAO) in salmon protein hydrolysates is known, but it requires excessive amounts of NADPH, an expensive cofactor. Here, we describe a cofactor regeneration system that allows using less cofactor in the enzyme-driven TMA removal process. This dual enzyme system removed 75% of TMA from a salmon protein hydrolysate, resulting in a significantly reduced fishy odor as confirmed by a trained sensory panel compared to the untreated control. This enzyme cascade is an important step toward making targeted TMA removal economically feasible for marine biomass valorization.

## Linked entities

- **Proteins:** Gld (Glucose dehydrogenase)
- **Chemicals:** trimethylamine (PubChem CID 1146), trimethylamine-N-oxide (PubChem CID 1145), NADPH (PubChem CID 5884), NADP+ (PubChem CID 5885)

## Full-text entities

- **Genes:** H6PD (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase) [NCBI Gene 9563] {aka CORTRD1, G6PDH, GDH, H6PDH}, FMO3 (flavin containing dimethylaniline monoxygenase 3) [NCBI Gene 2328] {aka FMOII, TMAU, dJ127D3.1}
- **Chemicals:** TMAO (MESH:C005855), mFMO (-), oxygen (MESH:D010100), amine (MESH:D000588), NADP+ (MESH:D009249), TMA (MESH:C023336)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12997807/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12997807/full.md

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Source: https://tomesphere.com/paper/PMC12997807