Natural pesticides
pyrethrins biosynthesized by Tanacetum cinrerariifolium are biodegradable and
safer insecticides for pest insect control. TcGLIP, a GDSL lipase
underpinning the ester bond formation in pyrethrins, exhibits high
stereo-specificity for acyl-CoA and alcohol substrates. However, it
is unknown how the enzyme recognizes the other structural features
of the substrates and whether such specificity affects the product
amount and composition in T. cinrerariifolium. We report here that the cysteamine moiety in (1R,3R)-chrysanthemoyl CoA and the conjugated diene
moiety in (S)-pyrethrolone play key roles in the
interactions with TcGLIP. CoA released from chrysanthemoyl CoA in
the pyrethrin-forming reaction reduces the substrate affinity for
TcGLIP by feedback inhibition. (S)-Pyrethrolone shows
the highest catalytic efficiency for TcGLIP, followed by (S)-cinerolone and (S)-jasmololone, contributing,
at least in part, to determine the pyrethrin compositions in T. cinerariifolium.
Pyrethrins from Tanacetum cinerariifolium are natural pesticides that exhibit high knockdown and killing activities against flying insects such as diseasespreading mosquitoes. Despite the increasing demand for pyrethrins, the mechanism of pyrethrin biosynthesis remains elusive. To elucidate it, we for the first time created pyrethrin mimetic phosphonates targeting the GDSL esterase/ lipase (GELP or TcGLIP) underpinning pyrethrin biosynthesis. The compounds were synthesized by reacting mono-alkyl or mono-benzyl-substituted phosphonic dichloride with pyrethrolone, the alcohol moiety of pyrethrin I and II, and then pnitrophenol. n-Pentyl (C5) and n-octyl (C8)-substituted compounds were the most potent of the (S) p ,(S) c , and (R) p ,(S) c diastereomers, respectively. The (S)pyrethrolonyl group is more effective than the (R)-pyrethrolonyl group in blocking TcGLIP, consistent with the features predicted by TcGLIP models complexed with the (S) p ,(S) c -C5 and (R) p ,(S) c -C8 probes. The (S) p ,(S) c -C5 compound suppressed pyrethrin production in T. cinerariifolium, demonstrating potential as a chemical tool for unravelling pyrethrin biosynthesis.
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