Abstract
Plant-parasitic nematodes ingest and convert host phytosterols via dealkylation to cholesterol for both structural and hormonal requirements. The insect 24-dehydrocholesterol reductase (DHCR24) was shown in vitro as a committed enzyme in the dealkylation via chemical blocking. However, an increased brood size and ovulation rate, instead compromised development, were observed in the engineered nematode Caenorhabditis elegans where the DHCR24 gene was knocked down, indicating the relationship between DHCR24 and dealkylation and their function in nematodes remains illusive. In this study, a defect in C. elegans DHCR24 causes impaired growth of the nematode with sitosterol (a major component of phytosterols) as a sole sterol source. Plant sterols with rationally designed structure (null substrates for dealkylation) can’t be converted to cholesterol in wild-type worms, and their development was completely halted. This study underpins the essential function of DHCR24 in nematodes and would be beneficial for the development of novel nematocidal strategies.
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The data that support the findings of this study are available from the corresponding author, upon reasonable request.
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We are grateful to the anonymous reviewers for their valuable improvement to this manuscript. This work was supported in part by grants from the National Key R&D Program of Chinas (2021YFA0909600 and 2021YFE0110100), the National Natural Science Foundation of China (32060061 and 32370380), the Key R&D Program of Hainan Province (ZDYF2022XDNY140), the Natural Science Foundation of Hainan Province (322QN250), the Foreign Expert Foundation of Hainan Province (G20230607016E), and the Program of Hainan Provincial Key Laboratory of Tropical Hydrobiotechnology (SWJS202205).
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QG, XC, LZ, WZ and YL conceived and planned the experiments. QG, XC and LZ carried out the experiments. QC and LZ contributed to sample preparation. XC, WZ and YL contributed to the interpretation of the results. YL took the lead in writing the manuscript. All authors provided critical feedback and helped shape the research, analysis, and manuscript.
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Gan, Q., Cui, X., Zhang, L. et al. Control Phytophagous Nematodes By Engineering Phytosterol Dealkylation Caenorhabditis elegans as a Model. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00869-x
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DOI: https://doi.org/10.1007/s12033-023-00869-x