Nicotinamide riboside production in filamentous fungi
Inventors
Emalfarb, Mark Aaron • Tchelet, Ronen • KOIVURANTA, Kari Tapio • Ilmén, Marja Hannele • Castillo, Sandra • Jouhten, Paula
Assignees
VTT Technical Research Centre of Finland • Dyadic International USA Inc
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Abstract
The present invention relates to genetically modified ascomycetous filamentous fungi, particularly of the species Thermothelomyces heterothallica, capable of producing elevated amounts of nicotinamide riboside.
Core Innovation
The invention relates to a genetically modified ascomycetous filamentous fungus, particularly Thermothelomyces heterothallica C1, for producing nicotinamide riboside or a precursor thereof. The fungal cell comprises three exogenous polynucleotides encoding SDT1, BNA6, and NMA1, combined with deleted or disrupted NRK1, NRT1, and PNP1 genes. This genetic modification enhances enzymes in the nicotinamide riboside pathway while reducing nicotinamide riboside catabolism or reuptake to increase target production.
Engineered strains produce increased nicotinamide riboside relative to parental or corresponding unmodified strains, with reported combined extracellular and intracellular levels reaching about 150 mg/L. Pathway engineering targets and production data characterize the metabolite profiles of the modified strains. Specific background problems are not explicitly described in the provided patent content.
Claims Coverage
The provided claims identify one independent claim directed to a genetically modified fungus, comprising one inventive feature.
Genetically modified fungus for nicotinamide riboside production
A genetically modified ascomycetous filamentous fungus for producing nicotinamide riboside or a precursor thereof, comprising at least one cell with three exogenous polynucleotides encoding SDT1, BNA6, and NMA1, and having deleted or disrupted NRK1, NRT1, and PNP1 genes.
The independent claim covers the specified genetically modified fungus comprising the combination of three exogenous polynucleotides and three disrupted or deleted genes for nicotinamide riboside production.
Stated Advantages
The engineered strains produce more nicotinamide riboside than parental or corresponding unmodified ascomycetous filamentous fungi cultured under similar conditions.
The summary identifies secreted nicotinamide riboside as an advantage.
The summary identifies reduced culture viscosity as an advantage.
The summary identifies industrial-scale fermentation as an advantage.
Documented Applications
Producing nicotinamide riboside or a precursor thereof using a genetically modified ascomycetous filamentous fungus.
Culturing the claimed fungus in a suitable medium and recovering the produced nicotinamide riboside product.
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