TY - JOUR
T1 - Synthetic biomimetic coenzymes and alcohol dehydrogenases for asymmetric catalysis
AU - Josa-Culleré, Laia
AU - Lahdenperä, Antti S.K.
AU - Ribaucourt, Aubert
AU - Höfler, Georg T.
AU - Gargiulo, Serena
AU - Liu, Yuan Yang
AU - Paradisi, Francesca
AU - Hollmann, Frank
AU - Paul, Caroline E.
AU - More Authors, null
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Alcohol dehydrogenases
KW - Cofactor regeneration
KW - Formate dehydrogenase
KW - Nicotinamide coenzyme biomimetics
KW - Rhodium catalyst
UR - http://www.scopus.com/inward/record.url?scp=85063501351&partnerID=8YFLogxK
U2 - 10.3390/catal9030207
DO - 10.3390/catal9030207
M3 - Article
SN - 2073-4344
VL - 9
JO - Catalysts
JF - Catalysts
IS - 3
M1 - 207
ER -