Synthetic Biomimetic Coenzymes and Alcohol Dehydrogenases for Asymmetric Catalysis

• Main Authors: Laia Josa-Culleré, Antti S. K. Lahdenperä, Aubert Ribaucourt, Georg T. Höfler, Serena Gargiulo, Yuan-Yang Liu, Jian-He Xu, Jennifer Cassidy, Francesca Paradisi, Diederik J. Opperman, Frank Hollmann, Caroline E. Paul
• Format: Article
• Language: English
• Published: MDPI AG 2019-02-01
• Series: Catalysts
• Subjects: alcohol dehydrogenases; cofactor regeneration; formate dehydrogenase; nicotinamide coenzyme biomimetics; rhodium catalyst
• Online Access: https://www.mdpi.com/2073-4344/9/3/207

Redox reactions catalyzed by highly selective nicotinamide-dependent oxidoreductases are rising to prominence in industry. The cost of nicotinamide adenine dinucleotide coenzymes has led to the use of well-established elaborate regeneration systems and more recently alternative synthetic biomimetic cofactors. These biomimetics are highly attractive to use with ketoreductases for asymmetric catalysis. In this work, we show that the commonly studied cofactor analogue 1-benzyl-1,4-dihydronicotinamide (BNAH) can be used with alcohol dehydrogenases (ADHs) under certain conditions. First, we carried out the rhodium-catalyzed recycling of BNAH with horse liver ADH (HLADH), observing enantioenriched product only with unpurified enzyme. Then, a series of cell-free extracts and purified ketoreductases were screened with BNAH. The use of unpurified enzyme led to product formation, whereas upon dialysis or further purification no product was observed. Several other biomimetics were screened with various ADHs and showed no or very low activity, but also no inhibition. BNAH as a hydride source was shown to directly reduce nicotinamide adenine dinucleotide (NAD) to NADH. A formate dehydrogenase could also mediate the reduction of NAD from BNAH. BNAH was established to show no or very low activity with ADHs and could be used as a hydride donor to recycle NADH.