重要杀菌剂与作用靶标的互作及调控机制

Interactional mechanism between fungicide active molecule and receptor/action target and regulatory mechanism of pathogen against fungicide stress are theoretical basis of creating high active, low toxic and selective fungicides, studying fungicide pharmacology and its efficient and reduced application technology. With Fusarium asiaticum causing wheat scab disease and general microtubulin inhibitor carbendazim as materials, with two important fungicide molecular targets of β1-tubulin and β2-tubulin as object, this project intends to study and reveal the molecular specific interaction mechanism between fungicide and two molecular targets using modern molecular biology technology, providing some theories for specially creating high active and selective microtubulin inhibitors based on microtubulins of different pest; to study the interaction between fungicide active molecule and microtubulin from natural variation and to reveal the genetic mechanism of pathogen with sensitivity and resistance variation, providing some theories for creating high active and anti-resistant fungicides; to study the regulatory mechanism of common fungicide-resistance mutation genotypes of microtubulin on fitness key properties such as drug-sensitivity, mycelial growth, reproduction and virulence, to reveal the genetic mechanism of drug-sensitivity difference in pathogen populations, providing the theoretic basis for high efficient utilization of fungicides and development of new and subversive resistance management technology.

杀菌剂化合物小分子与病原菌受体（作用靶标）的互作及菌体应对药物胁迫的调控机制是高效低毒选择性杀菌剂创制和杀菌剂药理学及增效减量应用技术研究的理论基础。本项目拟以引起小麦赤霉病的亚洲镰孢菌和常用微管蛋白抑制剂多菌灵为材料，以项目组前期发现的两个重要杀菌剂分子靶标β1-微管蛋白和β2-微管蛋白为对象，采用现代分子生物学技术研究和揭示这两个分子靶标与杀菌剂分子特异性互作机制，为针对不同有害生物的微管蛋白特异性创制超高活性的选择性抑制剂提供理论依据；研究自然变异的微管蛋白与药剂分子的互作，揭示病原菌发生过敏性和抗药性变异的遗传机制，为超高活性和反抗性药物创制提供理论基础；研究亚洲镰孢菌应对微管蛋白抑制剂胁迫的常见抗药性变异，对药理作用及生长、繁殖和致病力等适合度关键性状的调控机制，揭示重要作物病原真菌药敏性差异的遗传进化机制，为杀菌剂的高效利用及抗药性治理颠覆性新技术研发提供理论基础。

杀菌剂化合物小分子与病原菌药靶的互作及菌体应对药物胁迫的调控机制是高效低毒选择性杀菌剂创制和杀菌剂药理学及增效减量应用技术研究的理论基础。本项目以亚洲镰孢菌两个重要杀菌剂靶标β1微管蛋白和β2微管蛋白为研究对象，研究了微管蛋白互作模式及其与多菌灵的互作及调控机制；揭示了靶标蛋白发生变异与多菌灵的特异性互作机制，为高效、低毒、高选择性的靶向杀菌剂创制提供了理论依据；阐明了亚洲镰孢菌微管蛋白发生自然变异调控多菌灵过敏性与抗药性的遗传机制，为超高活性和反抗性药物创制提供了理论基础；探明了亚洲镰孢菌应对微管蛋白抑制剂多菌灵胁迫的常见抗药性变异对药敏性、生长、繁殖、致病力、DON毒素生物合成等关键生物适合度的调控机制，指导了杀菌剂的高效利用及抗药性治理颠覆性新技术研发；基于此，深入研究了井冈霉素在治理多菌灵抗性及抑制DON毒素生物合成的理论基础，揭示了井冈霉素与唑类杀菌剂协同使用的增效机理，指导了井冈霉素在多菌灵抗性治理与DON毒素污染控制上的创新应用，为井冈霉素与三唑类药剂协同防治小麦赤霉病、减少DON毒素污染、降低化学农药用量及治理杀菌剂抗性提供了科学依据，提高了我国植物病害防控的科技创新水平，保障了我国粮食安全与生态环境安全。