Journal
CHEMISTRY & BIOLOGY
Volume 19, Issue 12, Pages 1525-1534Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2012.10.002
Keywords
-
Categories
Funding
- National Institutes of Health [ES 001670]
Ask authors/readers for more resources
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 alpha/beta-hydrolase fold enzyme.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available