Enzymes to Regenerate NAD(P)+ from Inhibitory NAD(P)H Isomers

Nearly 20% of known oxidoreductases require cofactors to supply stoichiometric quantities of reducing equivalents. For the majority of these oxidoreductases, NAD(P)H is the required cofactor. Since the total pool of intracellular NAD(P)H and NAD(P)+ is relatively small, cofactor recycling is needed in the order of thousands to millions of cycles. We are developing an electrobioreactor for enzymatic transformations and ultimately leading to fermentation-based biotransformations. As shown in Figure 1, we are developing an electrochemical bioreactor that can be used both for enzymatic reactions and fermentation. Using this set-up, we are overcoming unproductive NAD(P)H isomers produced by electrochemical reduction using the enzyme renalase, which naturally salvages non-biologically relevant NAD(P)H isomers leading back to the oxidized NAD(P)+ for further use [Morrison et al. Biotechnol. Adv. 36, 120-131 (2018)] [Morrison et al. PLoS One 15, e0242109 (2020)].

Diagram depicting NADH isomer detoxificaton reactions catalyzed by renalase.

Figure 1: NADH isomer detoxification reactions catalyzed by renalase.

Current Collaborators:
Mattheos Koffas - Rensselaer Polytechnic Institute

James Swartz – Stanford University
William Armiger and David Dodds – SynAppBio, Inc.

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