Heterologous production of the widely used natural food colorant carminic acid in Aspergillus nidulans.

Autor: Frandsen RJN; Section for Synthetic Biology, Department of Biotechnology and Biomedicine, The Technical University of Denmark, Kongens Lyngby, Denmark. rasf@bio.dtu.dk., Khorsand-Jamal P; Section for Synthetic Biology, Department of Biotechnology and Biomedicine, The Technical University of Denmark, Kongens Lyngby, Denmark.; Chr. Hansen Natural Colors A/S, Hoersholm, Denmark.; Novo Nordisk A/S, Maaloev, Denmark., Kongstad KT; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. kenneth.kongstad@sund.ku.dk., Nafisi M; Chr. Hansen Natural Colors A/S, Hoersholm, Denmark.; Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark., Kannangara RM; Chr. Hansen Natural Colors A/S, Hoersholm, Denmark.; Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark.; River Stone Biotech ApS, København Ø, Fruebjergvej 3, 2100, Denmark., Staerk D; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Okkels FT; Chr. Hansen Natural Colors A/S, Hoersholm, Denmark.; Actabio ApS, Roskilde, Denmark., Binderup K; Chr. Hansen Natural Colors A/S, Hoersholm, Denmark.; DSM Nutritional Products, Kaiseraugst, Switzerland., Madsen B; Chr. Hansen Natural Colors A/S, Hoersholm, Denmark., Møller BL; Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark.; Center for Synthetic Biology, University of Copenhagen, Frederiksberg, Denmark., Thrane U; Section for Synthetic Biology, Department of Biotechnology and Biomedicine, The Technical University of Denmark, Kongens Lyngby, Denmark.; Department of Energy Performance, Indoor Environment and Sustainability, Danish Building Research Institute, Aalborg University Copenhagen, Copenhagen, Denmark., Mortensen UH; Section for Synthetic Biology, Department of Biotechnology and Biomedicine, The Technical University of Denmark, Kongens Lyngby, Denmark.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Aug 27; Vol. 8 (1), pp. 12853. Date of Electronic Publication: 2018 Aug 27.
DOI: 10.1038/s41598-018-30816-9
Abstrakt: The natural red food colorants carmine (E120) and carminic acid are currently produced from scale insects. The access to raw material is limited and current production is sensitive to fluctuation in weather conditions. A cheaper and more stable supply is therefore desirable. Here we present the first proof-of-concept of heterologous microbial production of carminic acid in Aspergillus nidulans by developing a semi-natural biosynthetic pathway. Formation of the tricyclic core of carminic acid is achieved via a two-step process wherein a plant type III polyketide synthase (PKS) forms a non-reduced linear octaketide, which subsequently is folded into the desired flavokermesic acid anthrone (FKA) structure by a cyclase and a aromatase from a bacterial type II PKS system. The formed FKA is oxidized to flavokermesic acid and kermesic acid, catalyzed by endogenous A. nidulans monooxygenases, and further converted to dcII and carminic acid by the Dactylopius coccus C-glucosyltransferase DcUGT2. The establishment of a functional biosynthetic carminic acid pathway in A. nidulans serves as an important step towards industrial-scale production of carminic acid via liquid-state fermentation using a microbial cell factory.
Databáze: MEDLINE
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