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Defeating Copper Tolerance: An Example of How 'Omics' Research Can Accelerate Discovery of New Wood Protection Compounds

机译:击败铜耐受性:“OMIC”研究如何加速发现新的木材保护化合物

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Imagine if you could measure all the genes being expressed at any one time in an organism and you knew what all the genes did in a cell. The power of this knowledge would allow you to determine how organisms regulate gene activity to survive. This isthe essence of how "omics" science accelerates biological understanding. From a wood protection standpoint, understanding which genes regulate copper tolerance effectively identifies metabolic chokepoints that would have the highest likelihood of interfering with copper tolerance. Thus, the search for copper co-biocides is no longer random, but instead, follows a rational process, guided by knowledge of which steps in metabolism are being differentially regulated for survival on substrates containing copper. We used this rational process to identify two potential inhibitors that might defeat copper tolerance: pyraclostrobin (a member of the strobilurin family of fungicides) and salicylhydroxamic acid (SHAM). The strobilurins and SHAM disrupt differentsteps in mitochondrial respiration, a metabolic pathway we found to be up-regulated with the biosynthesis of oxalate in our omics analysis. Oxalate is the molecule that has a direct role in removing copper toxicity by trapping the copper in an insolublecopper oxalate crystal. In accordance with our hypothesis, the triple combination of 5000 ug/mL copper sulfate, 4 or 8 ug/mL pyraclostrobin, and 100 ug/mL SHAM completely inhibited growth compared to compounds tested alone over a 20-day observation period in agar plate studies with the copper-tolerant fungus, Fibroporia radiculosa. Results from AWPA E22 soil block tests, which uses percent compression strength loss as a measure of decay, were also promising when tested against F. radiculosa and anothercopper-tolerant species, Fomitopsis palustris. Using above ground retentions for copper emanolamine, the triple combination wood treatment (copper, pyraclostrobin, and SHAM) performed much better than copper emanolamine alone, and performed as well or better than wood treated with our reference, the above ground retention for ACQ-D. With over 900 potential targets or genes that showed differential regulation for survival on copper, it is our hope that co-biocide discovery will no longer be the bottleneck in wood preservative development.
机译:想象一下,如果你可以测量在生物体中任何时间表达的所有基因,你都知道在细胞中所做的所有基因。这种知识的力量允许您确定生物体如何调节基因活性以存活。这是“OMICS”科学如何加速生物理解的本质。从木材保护角度来看,了解哪个基因调节铜耐受的理解有效地识别了对干扰铜耐受性的最高可能性的代谢池点。因此,对铜共生物的搜索不再是随机的,而是遵循理性过程,通过了解含有铜基材上的底物存活中代谢的步骤。我们使用这种合理的方法来鉴定可能破坏铜耐受性的两个潜在抑制剂:Pyraclostrobin(杀毒剂般的杀菌剂家族的成员)和水杨酰胺酸(假)。斯特罗脲和假扰动线粒体呼吸中的不同症,我们发现在我们的OMICS分析中以草酸盐的生物合成来调节代谢途径。草酸盐是通过在Insolublopper晶体中捕获铜来除去铜毒性的直接作用的分子。根据我们的假设,与单独在琼脂平板研究中的20天观察期间测试的化合物相比,5000 ug / ml硫酸铜,4或8μg/ ml吡咯磷脂和100ug / ml假的100ug / ml假的三倍组合完全抑制生长用铜耐用的真菌,纤维植物饺子。 AWPA E22土壤块试验结果,使用百分比压缩强度损失作为衰减的量度,在针对F. Radiculosa和Intepheropper耐受物种,Foritopsis Palustris的测试时也是有希望的。使用上述铜型氧化铜氧化铝的地面避孕,三联组合木材处理(铜,Pyraclostrobin和Sham)仅仅比铜氧吡胺更好地表现出,并且如我们参考所处理的,或者优于我们参考的木材进行,以上保留ACQ-D的地面保留。对于超过900个潜在的靶标或基因,表明铜的存活率差异调节,我们希望共和杀生物酰胺发现将不再是木材防腐发育的瓶颈。

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