Abstract
A synthetic biology approach to the rational design of analogues of olfactory ligands by providing unnatural substrates for the enzyme synthesising (S)-germacrene D, an olfactory ligand acting as a plant derived insect repellent, to produce novel ligands is described as a viable alternative to largely unsuccessful ligand docking studies. (S)-14,15-Dimethylgermacrene D shows an unexpected reversal in behavioural activity.
Highlights
A synthetic biology approach to the rational design of analogues of olfactory ligands by providing unnatural substrates for the enzyme synthesising (S)-germacrene D, an olfactory ligand acting as a plant derived insect repellent, to produce novel ligands is described as a viable alternative to largely unsuccessful ligand docking studies. (S)-14,15-Dimethylgermacrene D shows an unexpected reversal in behavioural activity
We test the hypothesis that, if a compound is accepted as an unnatural substrate by the enzyme that synthesises the natural ligand, the product is likely to demonstrate sufficient coverage of the chemical space associated with the natural ligand to be active
4a R1–R6 = H, R1–R6 = H for all others except as shown above. a Two products generated, one of which was 1b. b 15F-FDP gave multiple products that decomposed upon standing. c Percentage conversion and percentage conversion relative to natural substrate.[4] d Isolated yield after preparative scale incubation with GDS-Y406F. e Product was identified as 8-fluoro-a-humulene (5).[7] f Results from the electroantennograms are expressed as + = active, +++ = highly active. g Results from the olfactometer are expressed as À repellent, À À À highly repellent, +++ highly attractive, n/a = not active, n/t = not tested
Summary
A synthetic biology approach to the rational design of analogues of olfactory ligands by providing unnatural substrates for the enzyme synthesising (S)-germacrene D, an olfactory ligand acting as a plant derived insect repellent, to produce novel ligands is described as a viable alternative to largely unsuccessful ligand docking studies. (S)-14,15-Dimethylgermacrene D shows an unexpected reversal in behavioural activity. We test the hypothesis that, if a compound is accepted as an unnatural substrate by the enzyme that synthesises the natural ligand, the product is likely to demonstrate sufficient coverage of the chemical space associated with the natural ligand to be active.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
