This disclosure provides a method of synthesis of 4′-thioribose NAD+ and analogues thereof, using an efficient chemoenzymatic approach. Also provided are methods of inhibiting the CD38 enzyme and compounds including 4′-thioribose NAD+ and compounds related thereto.

Cancer combination therapies utilizing a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor in combination with a nicotinamide adenine dinucleotide (NAD) salvage pathway precursor are described. Cancers treated with the combination therapies can be nicotinamide riboside kinase (NMRK1) low cancers and/or Myc high cancers and can include various forms of glioblastomas.

A method of making nicotinamide mononucleotide (NMN), nicotinamide mononucleotide derivatives, or mixtures thereof is disclosed. The method involves the in vitro artificial enzymatic pathways comprised: the generation of alpha-D-ribose-1-phosphate from numerous substrates followed by the synthesis of nicotinamide mononucleotide catalyzed by nicotinamide riboside phosphorylase and nicotinamide riboside kinase or the generation of 5-phospho-alpha-D-ribose-1-diphosphate from nucleotides followed by the synthesis of nicotinamide mononucleotide catalyzed by nicotinamide phosphoribosyltransferase. The multiple enzymes were reconstituted in one pot, wherein in-situ removal of byproducts that can be converted to other non-inhibitory chemicals with supplementary enzymes push the overall biotransformation toward the synthesis of nicotinamide mononucleotide. Furthermore, nicotinamide mononucleotide can be converted to its derivatives—nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.

The present invention relates to the field of biotechnologies. Disclosed are an enzyme composition for preparing ?-nicotinamide mononucleotide (NMN), and an application thereof. In the present invention, by using adenosine and nicotinamide as raw materials, D-ribose 1-phosphate and a nicotinamide ribose intermediate are generated under enzyme catalysis of an enzyme composition of a PNP enzyme and an NRK enzyme, and finally NMN is obtained; only two enzymes need to be involved in the whole reaction system, and the by-product adenine can be recycled. Moreover, only one molecule of ATP needs to be consumed for generating one molecule of NMN, thereby greatly reducing the process cost. The reaction of synthesizing NMN by NRK enzyme catalysis in the last step is irreversible, and thus, the substrate conversion rate can be greatly improved and the production cost can be further reduced.