title: The biosynthetic pathway for a thousand-year-old natural food colorant and citrinin in Penicillium marneffei.
abstract: Monascorubrin and its derivatives are polyketides used as natural colorants for a wide range of food for more than one thousand years. Since the biosynthetic pathway for this ancient chemical compound is unknown and genome sequence unavailable for any Monascus species, monascorubrin production has relied on extraction from fungal cultures of Monascus species. In vitro synthesis and genetic manipulation are not possible. Here we report the polyketide gene cluster and pathway for monascorubrin biosynthesis in Penicillium marneffei, a diffusible red pigment-producing, thermal dimorphic fungus, taking advantage of available genome sequence and faster growth rate than Monascus species. We also documented that the red pigment of P. marneffei is a mixture of more than 16 chemical compounds, which are amino acid conjugates of monascorubrin and rubropunctatin, and showed that this polyketide gene cluster and pathway are also responsible for biosynthesis of ankaflavin and citrinin, a mycotoxin with nephrotoxic activity in mammals. The present study on elucidation of the biosynthetic pathway of monascorubrin is a proof-of-the-concept study that serves as a cornerstone for future studies on monascorubrin biosynthesis pathway dissection in Monascus species.
authors.affiliation: 1] Department of Microbiology, The University of Hong Kong, Hong Kong [2] State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong [3] Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong [4] Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong.
authors.forename: Patrick C Y
authors.initials: PC
authors.lastname: Woo
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong.
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong.
authors.forename: Emily W T
authors.initials: EW
authors.lastname: Tam
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong.
authors.forename: Kim-Chung
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong.
authors.forename: Karrie K Y
authors.initials: KK
authors.lastname: Yung
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong.
authors.forename: Chris K F
authors.initials: CK
authors.lastname: Leung
authors.affiliation: 1] Department of Microbiology, The University of Hong Kong, Hong Kong [2] State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong [3] Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong [4] Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong.
authors.forename: Kong-Hung
authors.initials: KH
authors.lastname: Sze
authors.affiliation: 1] Department of Microbiology, The University of Hong Kong, Hong Kong [2] State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong [3] Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong [4] Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong.
authors.forename: Susanna K P
authors.initials: SK
authors.lastname: Lau
authors.affiliation: 1] Department of Microbiology, The University of Hong Kong, Hong Kong [2] State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong [3] Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong [4] Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000596:Amino Acids / Q000235:genetics; D053898:Biosynthetic Pathways / Q000235:genetics; D002874:Chromosome Mapping; D002953:Citrinin / Q000096:biosynthesis* / Q000378:metabolism; D005505:Food Coloring Agents / Q000378:metabolism*; D016681:Genome, Fungal; D006575:Heterocyclic Compounds, 3-Ring / Q000378:metabolism*; D005810:Multigene Family; D010407:Penicillium / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D005505:Food Coloring Agents; D006575:Heterocyclic Compounds, 3-Ring; D002953:Citrinin; C522768:monascorubrin