Conserved RHR Motif Enables Widespread Use Of Non-Canonical Redox Cofactors In Aldehyde Dehydrogenases

Brief Description

This technology improves enzymatic activity and biomanufacturing cost by engineering a conserved motif into enzymes and utilizing low-cost non-canonical redox cofactors.

Full Description

Biomanufacturing relies on enzymes and cells to produce fuels, materials, medicines, and foods, however, the enzymes use costly natural redox cofactors (NAD(P)+) with inherent electron delivery issues. This technological invention identifies a conserved sequence motif that enables a class of enzymes to bind and utilize non-canonical redox cofactors (NRC), which are more cost-effective than NAD(P)+. One-third of these enzymes naturally contain this motif, whereas for the remaining two-thirds, introducing the motif enhanced their NRC activity by up to 60-fold, surpassing the performance of nearly all known natural and previously engineered NRC-active enzymes. The motif can be transferred into diverse enzymes to significantly boost their NRC activity, enabling precise enzyme design and modification for superior low-cost biomanufacturing performance.

Suggested uses

• Cost-effective biomanufacturing of fuels, chemicals, and specialty materials 
• Industrial biocatalysis requiring efficient electron transfer 
• Pharmaceutical production involving enzyme-mediated synthesis 
• Food and beverage industries leveraging enzyme transformations

Advantages

• Enables use of low-cost, biomimetic non-canonical redox cofactors (NRCs) 
• Significantly enhances enzyme activity towards NRCs by up to 60-fold 
• Transferable motif allows broad enzyme engineering and customization 
• Improves electron delivery precision in biocatalytic processes 
• Reduces reliance on expensive natural cofactors like NAD(P)+

Patent Status

Patent Pending

Related Materials

• Saleh S et al. A Sequence Motif Enables Widespread Use of Non-Canonical Redox Cofactors in Natural Enzymes. bioRxiv [Preprint]. Doi: 10.1101/2025.08.01.668186.