Resorcylic acid lactone biosynthesis relies on a stereotolerant macrocyclizing thioesterase.
Zearalenone and radicicol are highly related resorcylic acid lactones with the rare property of having opposite stereochemical configurations of the secondary alcohol involved in lactone formation. The ability of the thioesterases from the zearalenone and radicicol biosynthetic pathways to macrocyclize both D and L configured synthetic substrate analogs was biochemically characterized and showed that both enzymes were highly stereotolerant, macrocyclizing both substrates with similar kinetic parameters. This observed stereotolerance is consistent with a proposed evolution of both natural products from a common ancestral resorcylic acid lactone.
Department of Chemistry, Centre for Catalysis Research and Innovation, University of Ottawa , Ottawa, ON K1N 6N5, Canada.
Graham W
GW
Heberlig
Monica
M
Wirz
Meng
M
Wang
Christopher N
CN
Boddy
D053898:Biosynthetic Pathways; D005658:Fungi / Q000201:enzymology / Q000378:metabolism; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry*; D015394:Molecular Structure; D048630:Polyketide Synthases / Q000378:metabolism*; D012118:Resorcinols / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D015025:Zearalenone / Q000031:analogs & derivatives / Q000737:chemistry*
D007783:Lactones; D018942:Macrolides; D012118:Resorcinols; D015025:Zearalenone; D048630:Polyketide Synthases; C035359:monorden