A sequence motif enables widespread use of noncanonical redox cofactors in natural enzymes.
- Open access
A conserved RH/QxxR motif enables widespread use of noncanonical redox cofactors in natural enzymes, with Bos taurus ALDH3a1 achieving unprecedented turnover with NMN+.
- Why it matters: Expanding the use of low-cost, versatile noncanonical redox cofactors (NRCs) could revolutionize biomanufacturing, but limited enzyme compatibility has hindered their adoption. Understanding how natural enzymes can efficiently utilize NRCs is crucial for developing cost-effective biocatalysts.
- What they did: Screening the aldehyde dehydrogenase family identified a conserved motif that enhances NRC activity; structural analysis revealed its role in cofactor positioning, and introducing this motif into various ALDH scaffolds increased NMN+ activity up to 60-fold.
- The result: This discovery provides a blueprint for engineering NRC-active enzymes, unlocking latent evolutionary potential and enabling the development of more efficient, cost-effective biocatalysts for industrial applications.