Montesinos Emilio, Bardají Eduard
Institute of Food and Agricultural Technology-CIDSAV-XaRTA, University of Girona, Campus Montilivi, E-18071 Girona.
Chem Biodivers. 2008 Jul;5(7):1225-37. doi: 10.1002/cbdv.200890111.
There is a need of antimicrobial compounds in agriculture for plant-disease control, with low toxicity and reduced negative environmental impact. Antimicrobial peptides are produced by living organisms and offer strong possibilities in agriculture because new compounds can be developed based on natural structures with improved properties of activity, specificity, biodegradability, and toxicity. Design of new molecules has been achieved using combinatorial-chemistry procedures coupled to high-throughput screening systems and data processing with design-of-experiments (DOE) methodology to obtain QSAR equation models and optimized compounds. Upon selection of best candidates with low cytotoxicity and moderate stability to protease digestion, anti-infective activity has been evaluated in plant-pathogen model systems. Suitable compounds have been submitted to acute toxicity testing in higher organisms and exhibited a low toxicity profile in a mouse model. Large-scale production can be achieved by solution organic or chemoenzymatic procedures in the case of very small peptides, but, in many cases, production can be performed by biotechnological methods using genetically modified microorganisms (fermentation) or transgenic crops (plant biofactories).
农业领域需要用于植物病害防治的抗菌化合物,这类化合物应具有低毒性并减少对环境的负面影响。抗菌肽由生物体产生,在农业中具有很大潜力,因为可以基于天然结构开发新的化合物,这些新化合物具有改进的活性、特异性、生物降解性和毒性等特性。利用组合化学程序结合高通量筛选系统以及采用实验设计(DOE)方法进行数据处理来设计新分子,以获得定量构效关系(QSAR)方程模型和优化的化合物。在选择具有低细胞毒性和对蛋白酶消化具有适度稳定性的最佳候选物后,已在植物病原体模型系统中评估了抗感染活性。合适的化合物已在高等生物中进行急性毒性测试,并在小鼠模型中显示出低毒性特征。对于非常小的肽,可以通过溶液有机或化学酶促程序实现大规模生产,但在许多情况下,可以通过使用转基因微生物(发酵)或转基因作物(植物生物工厂)的生物技术方法进行生产。