Tungsten Enzyme Using Hydrogen as an Electron Donor to Reduce Carboxylic Acids and NAD+

Tungsten-dependent aldehyde oxidoreductases (AORs) catalyze the oxidation of aldehydes to acids and are the only known enzymes reducing non-activated acids using electron donors with low redox potentials. We report here that AOR from Aromatoleum atomaticum (AOR(Aa)) catalyzes the reduction of organic acids not only with low-potential Eu(II) or Ti(III) complexes but also with H-2 as an electron donor. Additionally, AOR(Aa) catalyzes the H-2-dependent reduction of NAD(+) or benzyl viologen. The rate of H-2-dependent NAD(+) reduction equals to 10% of that of aldehyde oxidation, representing the highest H-2 turnover rate observed among the Mo/W enzymes. As AOR(Aa) simultaneously catalyzes the reduction of acids and NAD(+), we designed a cascade reaction utilizing a NAD(P)H-dependent alcohol dehydrogenase to reduce organic acids to the corresponding alcohols with H-2 as the only reductant The newly discovered W-hydrogenase side activity of AOR(Aa) may find applications in either NADH recycling or conversion of carboxylic acids to more useful biochemicals.

Automated summary

AOR(Aa) enzyme can catalyze the reduction reaction of organic acids using H-2 as an electron donor, and also catalyze the H-2-dependent reduction reaction of NAD(+) and benzyl viologen. This discovery has potential applications in the design of cascade reactions for the reduction of organic acids to alcohols.