2. Academic Validation
  3. Heterologous production of the widely used natural food colorant carminic acid in Aspergillus nidulans

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

  • Sci Rep. 2018 Aug 27;8(1):12853. doi: 10.1038/s41598-018-30816-9.
Rasmus J N Frandsen 1,  Paiman Khorsand-Jamal 2 3 4,  Kenneth T Kongstad 5,  Majse Nafisi 3 6,  Rubini M Kannangara 3 6 7,  Dan Staerk 8,  Finn T Okkels 3 9,  Kim Binderup 3 10,  Bjørn Madsen 3,  Birger Lindberg Møller 6 11,  Ulf Thrane 2 12,  Uffe H Mortensen 2
Affiliations

Affiliations

  • 1 Section for Synthetic Biology, Department of Biotechnology and Biomedicine, The Technical University of Denmark, Kongens Lyngby, Denmark. rasf@bio.dtu.dk.
  • 2 Section for Synthetic Biology, Department of Biotechnology and Biomedicine, The Technical University of Denmark, Kongens Lyngby, Denmark.
  • 3 Chr. Hansen Natural Colors A/S, Hoersholm, Denmark.
  • 4 Novo Nordisk A/S, Maaloev, Denmark.
  • 5 Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. kenneth.kongstad@sund.ku.dk.
  • 6 Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark.
  • 7 River Stone Biotech ApS, København Ø, Fruebjergvej 3, 2100, Denmark.
  • 8 Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • 9 Actabio ApS, Roskilde, Denmark.
  • 10 DSM Nutritional Products, Kaiseraugst, Switzerland.
  • 11 Center for Synthetic Biology, University of Copenhagen, Frederiksberg, Denmark.
  • 12 Department of Energy Performance, Indoor Environment and Sustainability, Danish Building Research Institute, Aalborg University Copenhagen, Copenhagen, Denmark.
PMID: 30150747 DOI: 10.1038/s41598-018-30816-9
Abstract

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.

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