Dataset Information

Creating Pyrethrin Mimetic Phosphonates as Chemical Genetics Tools Targeting the GDSL Esterase/Lipase TcGLIP to Investigate Pyrethrin Biosynthesis.

ABSTRACT: Pyrethrins from Tanacetum cinerariifolium are natural pesticides that exhibit high knockdown and killing activities against flying insects such as disease-spreading 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 p-nitrophenol. 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.

SUBMITTER: Matsuo N

PROVIDER: S-EPMC10291546 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Creating Pyrethrin Mimetic Phosphonates as Chemical Genetics Tools Targeting the GDSL Esterase/Lipase TcGLIP to Investigate Pyrethrin Biosynthesis.

Matsuo Noritada N Sugisaka Yukimi Y Aoyama Shiori S Ihara Makoto M Shinoyama Harue H Hosokawa Munetaka M Kamakura Yoshinobu Y Tanaka Daisuke D Tanabe Yoo Y Matsuda Kazuhiko K

Journal of medicinal chemistry 20230613 12

Pyrethrins from <i>Tanacetum cinerariifolium</i> are natural pesticides that exhibit high knockdown and killing activities against flying insects such as disease-spreading 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 mon ...[more]

PMID: 37309671

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Project description:GDSL-type esterase/lipase proteins (GELPs) belong to the SGNH hydrolase superfamily and contain a conserved GDSL motif at their N-terminus. GELPs are widely distributed in nature, from microbes to plants, and play crucial roles in growth and development, stress responses and pathogen defense. However, the identification and functional analysis of GELP genes are hardly explored in soybean. This study describes the identification of 194 GELP genes in the soybean genome and their phylogenetic classification into 11 subfamilies (A-K). GmGELP genes are disproportionally distributed on 20 soybean chromosomes. Large-scale WGD/segmental duplication events contribute greatly to the expansion of the soybean GDSL gene family. The Ka/Ks ratios of more than 70% of duplicated gene pairs ranged from 0.1-0.3, indicating that most GmGELP genes were under purifying selection pressure. Gene structure analysis indicate that more than 74% of GmGELP genes are interrupted by 4 introns and composed of 5 exons in their coding regions, and closer homologous genes in the phylogenetic tree often have similar exon-intron organization. Further statistics revealed that approximately 56% of subfamily K members contain more than 4 introns, and about 28% of subfamily I members consist of less than 4 introns. For this reason, the two subfamilies were used to simulate intron gain and loss events, respectively. Furthermore, a new model of intron position distribution was established in current study to explore whether the evolution of multi-gene families resulted from the diversity of gene structure. Finally, RNA-seq data were used to investigate the expression profiles of GmGELP gene under different tissues and multiple abiotic stress treatments. Subsequently, 7 stress-responsive GmGELP genes were selected to verify their expression levels by RT-qPCR, the results were consistent with RNA-seq data. Among 7 GmGELP genes, GmGELP28 was selected for further study owing to clear responses to drought, salt and ABA treatments. Transgenic Arabidopsis thaliana and soybean plants showed drought and salt tolerant phenotype. Overexpression of GmGELP28 resulted in the changes of several physiological indicators, which allowed plants to adapt adverse conditions. In all, GmGELP28 is a potential candidate gene for improving the salinity and drought tolerance of soybean.

Project description:BackgroundGDSL esterase/lipases (GELPs) play important roles in plant growth, development, and response to biotic and abiotic stresses. Presently, an extensive and in-depth analysis of GELP family genes in cotton is still not clear enough, which greatly limits the further understanding of cotton GELP function and regulatory mechanism.ResultsA total of 389 GELP family genes were identified in three cotton species of Gossypium hirsutum (193), G. arboreum (97), and G. raimondii (99). These GELPs could be classified into three groups and eight subgroups, with the GELPs in same group to have similar gene structures and conserved motifs. Evolutionary event analysis showed that the GELP family genes tend to be diversified at the spatial dimension and certain conservative at the time dimension, with a trend of potential continuous expansion in the future. The orthologous or paralogous GELPs among different genomes/subgenomes indicated the inheritance from genome-wide duplication during polyploidization, and the paralogous GELPs were derived from chromosomal segment duplication or tandem replication. GELP genes in the A/D subgenome underwent at least three large-scale replication events in the evolutionary process during the period of 0.6-3.2 MYA, with two large-scale evolutionary events between 0.6-1.8 MYA that were associated with tetraploidization, and the large-scale duplication between 2.6-9.1 MYA that occurred during diploidization. The cotton GELPs indicated diverse expression patterns in tissue development, ovule and fiber growth, and in response to biotic and abiotic stresses, combining the existing cis-elements in the promoter regions, suggesting the GELPs involvements of functions to be diversification and of the mechanisms to be a hormone-mediated manner.ConclusionsOur results provide a systematic and comprehensive understanding the function and regulatory mechanism of cotton GELP family, and offer an effective reference for in-depth genetic improvement utilization of cotton GELPs.

Project description:BACKGROUND:GDSL esterases/lipases are a newly discovered subclass of lipolytic enzymes that are very important and attractive research subjects because of their multifunctional properties, such as broad substrate specificity and regiospecificity. Compared with the current knowledge regarding these enzymes in bacteria, our understanding of the plant GDSL enzymes is very limited, although the GDSL gene family in plant species include numerous members in many fully sequenced plant genomes. Only two genes from a large rice GDSL esterase/lipase gene family were previously characterised, and the majority of the members remain unknown. In the present study, we describe the rice OsGELP (Oryza sativa GDSL esterase/lipase protein) gene family at the genomic and proteomic levels, and use this knowledge to provide insights into the multifunctionality of the rice OsGELP enzymes. RESULTS:In this study, an extensive bioinformatics analysis identified 114 genes in the rice OsGELP gene family. A complete overview of this family in rice is presented, including the chromosome locations, gene structures, phylogeny, and protein motifs. Among the OsGELPs and the plant GDSL esterase/lipase proteins of known functions, 41 motifs were found that represent the core secondary structure elements or appear specifically in different phylogenetic subclades. The specification and distribution of identified putative conserved clade-common and -specific peptide motifs, and their location on the predicted protein three dimensional structure may possibly signify their functional roles. Potentially important regions for substrate specificity are highlighted, in accordance with protein three-dimensional model and location of the phylogenetic specific conserved motifs. The differential expression of some representative genes were confirmed by quantitative real-time PCR. The phylogenetic analysis, together with protein motif architectures, and the expression profiling were analysed to predict the possible biological functions of the rice OsGELP genes. CONCLUSIONS:Our current genomic analysis, for the first time, presents fundamental information on the organization of the rice OsGELP gene family. With combination of the genomic, phylogenetic, microarray expression, protein motif distribution, and protein structure analyses, we were able to create supported basis for the functional prediction of many members in the rice GDSL esterase/lipase family. The present study provides a platform for the selection of candidate genes for further detailed functional study.

Dataset Information

Creating Pyrethrin Mimetic Phosphonates as Chemical Genetics Tools Targeting the GDSL Esterase/Lipase TcGLIP to Investigate Pyrethrin Biosynthesis.

Publications

Creating Pyrethrin Mimetic Phosphonates as Chemical Genetics Tools Targeting the GDSL Esterase/Lipase TcGLIP to Investigate Pyrethrin Biosynthesis.

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