Biosynthesis of lactones from diols mediated by an artificial flavin

Background Lactones are important compounds in the field of medicine, material and chemical industry. One of the promising accesses to these flexible scaffolds is NAD(P)+-dependent alcohol dehydrogenases-catalyzed oxidative lactonization of diols, which relies on the construction of an efficient NAD(P)+ regeneration system. Results In this study, a novel system combining horse liver alcohol dehydrogenase (HLADH) with the synthetic bridged flavin cofactor was established for biosynthesis of lactones. The reaction conditions of this system were optimized and a variety of lactones including chiral lactones were efficiently obtained from various diols. Compared to the previously reported NAD(P)+-regeneration systems, this system showed better regeneration efficiency and product yield. A two-phase system was further applied to solve the problem of product inhibition, and 80% yield was obtained at the condition of 300 mM substrate. Conclusions This study provides an efficient method to synthesis of lactones from diols under mild conditions. We believe this system will be a promising alternative to promote the synthesis of other valuable compounds. Graphic abstract

Biosynthesis of Lactones From Diols Mediated by an Artificial Flavin

Background: Lactones are important compounds in the field of medicine, material and chemical industry. One of the promising accesses to these flexible scaffolds is NAD(P)+-dependent alcohol dehydrogenases-catalyzed oxidative lactonization of diols, which relies on the construction of an efficient NAD(P)+ regeneration system. Results: In this study, a novel system combining horse liver alcohol dehydrogenase (HLADH) with the synthetic bridged flavin cofactor was established for biosynthesis of lactones. The reaction conditions of this system were optimized and a variety of lactones including chiral lactones were efficiently obtained from various diols. Compared to the previously reported NAD(P)+-regeneration systems, this system showed better regeneration efficiency and product yield. A two-phase system was further applied to solve the problem of product inhibition, and 80% yield was obtained at the condition of 300 mM substrate.Conclusions: This study provides an efficient method to synthesis of lactones from diols under mild conditions. We believe this system will be a promising alternative to promote the synthesis of other valuable compounds.

Effect of methylsulfonylmethane on oxidative stress and CYP3A93 expression in fetal horse liver cells

Objective: Stress-induced cytotoxicity caused by xenobiotics and endogenous metabolites induces the production of reactive oxygen species and often results in damage to cellular components such as DNA, proteins, and lipids. The cytochrome P450 (CYP) family of enzymes are most abundant in hepatocytes, where they play key roles in regulating cellular stress responses. We aimed to determine the effects of the antioxidant compound, methylsulfonylmethane (MSM), on oxidative stress response, and study the cytochrome P450 family 3 subfamily A (<i>CYP3A</i>) gene expression in fetal horse hepatocytes.Methods: The expression of hepatocyte markers and <i>CYP3A</i> family genes (<i>CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96</i>, and <i>CYP3A97</i>) were assessed in different organ tissues of the horse and fetal horse liver-derived cells (FHLCs) using quantitative reverse transcription polymerase chain reaction. To elucidate the antioxidant effects of MSM on FHLCs, cell viability, levels of oxidative markers, and gene expression of <i>CYP3A</i> were investigated in H₂O₂-induced oxidative stress in the presence and absence of MSM.Results: FHLCs exhibited features of liver cells and simultaneously maintained the typical genetic characteristics of normal liver tissue; however, the expression profiles of some liver markers and <i>CYP3A</i> genes, except that of <i>CYP3A93</i>, were different. The expression of <i>CYP3A93</i> specifically increased after the addition of H₂O₂ to the culture medium. MSM treatment reduced oxidative stress as well as the expression of <i>CYP3A93</i> and heme oxygenase 1, an oxidative marker in FHLCs.Conclusion: MSM could reduce oxidative stress and hepatotoxicity in FHLCs by altering <i>CYP3A93</i> expression and related signaling pathways.

1,4-NADH Biomimetic Co-Factors with Horse Liver Alcohol Dehydrogenase (HLADH), Utilizing [Cp*Rh(bpy)H](OTf) for Co-factor Regeneration, Do in Fact, Produce Chiral Alcohols from Reactions with Achiral Ketones

In this Catalysts Comment Article, we will present our latest published results [...]

Synthetic Biomimetic Coenzymes and Alcohol Dehydrogenases for Asymmetric Catalysis

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.

An effective hybrid strategy for converting rice straw to furoic acid by tandem catalysis via Sn-sepiolite combined with recombinant E. coli whole cells harboring horse liver alcohol dehydrogenase

The upgrading of biomass-derived furfural into high-value bio-based chemicals has attracted interest.