Kim J H, Campbell B C, Mahoney N, Chan K L, Molyneux R J, May G S
Plant Mycotoxin Research Unit, Western Regional Research Center, USDA-ARS, Albany, CA 94710, USA.
Lett Appl Microbiol. 2007 Aug;45(2):134-41. doi: 10.1111/j.1472-765X.2007.02159.x.
Identify natural products that effectively target antioxidative signal transduction/stress response systems [i.e., mitogen-activated protein kinase (MAPK) pathway, mitochondrial superoxide dismutase (Mn-SOD)] of fungi. Enhance activity of strobilurin or fludioxonil with discovered compounds.
Enhancement of antifungal activity of strobilurins, inhibitors of complex III of the mitochondrial respiratory chain, was tested using berberine hemisulfate and different phenolic compounds. The Saccharomyces cerevisiae sod2Delta, a deletion mutant lacking Mn-SOD gene, was highly sensitive to berberine and veratraldehyde. Functional complementation analysis verified these compounds target Mn-SOD. Activity of strobilurin (25-50 micromol l(-1)) was elevated on most aspergilli and Penicillium expansum by co-application with berberine or veratraldehyde (2-4 mmol l(-1)). These compounds also prevented Aspergillus fumigatus MAPK mutants (sakADelta and mpkCDelta) from escaping toxicity of fludioxonil (a phenylpyrrole fungicide potentiated by the MAPK pathway), a typical phenotype of fungal MAPK mutants.
Strobilurin activity or prevention of fungal escape from fludioxonil toxicity can be enhanced by co-application of certain alkaloids or phenolics.
Natural products can be used to target cellular stress response systems in fungal pathogens and serve as alternatives/additives to commercial antifungal agents.
鉴定可有效靶向真菌抗氧化信号转导/应激反应系统[即丝裂原活化蛋白激酶（MAPK）途径、线粒体超氧化物歧化酶（Mn-SOD）]的天然产物。用发现的化合物增强嘧菌酯或咯菌腈的活性。
使用半硫酸黄连素和不同的酚类化合物测试了线粒体呼吸链复合物III抑制剂嘧菌酯的抗真菌活性增强情况。酿酒酵母sod2Δ，即缺乏Mn-SOD基因的缺失突变体，对黄连素和藜芦醛高度敏感。功能互补分析证实这些化合物靶向Mn-SOD。通过与黄连素或藜芦醛（2 - 4 mmol·l⁻¹）共同施用，嘧菌酯（25 - 50 μmol·l⁻¹）对大多数曲霉菌和扩展青霉的活性有所提高。这些化合物还能防止烟曲霉MAPK突变体（sakAΔ和mpkCΔ）逃避咯菌腈（一种由MAPK途径增强活性的苯基吡咯类杀菌剂）的毒性，这是真菌MAPK突变体的典型表型。
通过共同施用某些生物碱或酚类化合物可增强嘧菌酯的活性或防止真菌逃避咯菌腈的毒性。
天然产物可用于靶向真菌病原体中的细胞应激反应系统，并可作为商业抗真菌剂的替代品/添加剂。
