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Title: Characterization of a fungal thioesterase having Claisen cyclase and deacetylase activities in melanin biosynthesis.

Authors: Vagstad, Anna L; Hill, Eric A; Labonte, Jason W; Townsend, Craig A

Published In Chem Biol, (2012 Dec 21)

Abstract: Melanins are a broad class of darkly pigmented macromolecules formed by oxidative polymerization of phenolic monomers. In fungi, melanins are known virulence factors that contribute to pathogenicity. Their biosynthesis generally involves polymerization of 1,8-dihydroxynaphthalene via a 1,3,6,8-tetrahydroxynaphthalene (THN) precursor assembled by multidomain, nonreducing polyketide synthases. Convergent routes to THN have evolved in fungi. Parallel heptaketide and hexaketide pathways exist that utilize conventional C-terminal thioesterase/Claisen cyclase domains and separate side-chain deacylases. Here, in vitro characterization of Pks1 from Colletotrichum lagenarium establishes a true THN synthase with a bifunctional thioesterase (TE) catalyzing both cyclization and deacetylation of an enzyme-bound hexaketide substrate. Chimeric TE domains were generated by swapping lid regions of active sites between classes of melanin TEs to gain insight into this unprecedented catalysis of carbon-carbon bond making and breaking by an α/β-hydrolase fold enzyme.

PubMed ID: 23261597 Exiting the NIEHS site

MeSH Terms: Amino Acid Sequence; Catalytic Domain; Colletotrichum/chemistry; Colletotrichum/enzymology*; Cyclization; Melanins/metabolism*; Models, Molecular; Molecular Sequence Data; Protein Structure, Tertiary; Sequence Alignment; Thiolester Hydrolases/chemistry*; Thiolester Hydrolases/metabolism*

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