Biosynthesis and mode of action of a new antifungal antibiotic produced by bacterial plant pathogens and rhizosphere bacteria

全球人口正在增加，估计到本世纪中叶将达到约90亿。对人类和动物粮食作物的需求将随着这一增长率而增加，除非我们能够显著提高作物产量，减少因疾病和腐败造成的作物损失，或者最好两者兼而有之，否则我们的粮食安全将受到损害。最近的研究表明，真菌（和卵菌）植物病原体在引起植物病害，减少作物产量或导致收获的粮食作物腐败方面发挥着越来越重要的作用。目前的作物保护方法涉及多种方法，包括使用一些由污染化学物质制成的农药，这些农药可能会对环境产生不良影响。本项目将涉及研究一种新型抗真菌分子，该分子由与植物密切相关的某些细菌自然产生。这种天然的抗真菌抗生素对一系列杀死包括农作物在内的真菌是致命的，因此它可能有助于预防或限制农作物疾病，而无需求助于合成有毒农药。已经在从环境中分离的一系列细菌中发现了负责形成这种新的天然抗真菌分子的基因，并且已经提出了活性分子生物合成的假设途径。我们将使用细菌遗传学和生理学方法过量生产这种新分子，然后纯化抗真菌药物，尝试使用一系列化学和物理方法确定抗生素的化学结构。我们将研究这种新抗生素是如何在产生它的细菌中组装的。我们已经证明，这种抗真菌抗生素除了能杀死引起植物疾病的真菌外，还能杀死简单的酵母（裂变酵母）。简单的酵母很容易使用遗传学和分子生物学方法进行研究，因此我们打算通过研究酵母细胞中新抗真菌剂的细胞靶点来利用这一点。我们希望这些信息也将直接与确定植物病原真菌中分子靶标的性质相关，这将有助于我们在未来开发不同的天然和半合成分子，这些分子可以保护作物免受疾病和腐败的影响，从而提高我们的粮食安全。

The global human population is increasing and it is estimated to reach around 9 Billion by mid-century. Demand for human and animal food crops will increase in line with this growth rate and our food security will be compromised unless we can significantly increase crop productivity, decrease crop losses due to disease and spoilage - or, preferably, both. Recent research has shown that fungal (and oomycete) plant pathogens play increasingly important roles in causing plant diseases that reduce crop production or lead to spoilage of harvested food crops. Current crop protection methods involve various approaches, including the use of some pesticides made by polluting chemistry that can have undesirable environmental impacts.This project will involve a study of a novel antifungal molecule(s) that is made naturally by some species of bacteria that live in close association with plants. This naturally-made antifungal antibiotic is lethal to a range of fungi that kill pants, including crop plants, and so it might be useful in preventing or limiting crop diseases without recourse to synthetic toxic pesticides. The genes responsible for the formation of this new natural antifungal molecule have been discovered in a range of bacteria isolated from the environment and a hypothetical pathway to biosynthesis of the active molecule has been suggested. We will overproduce this new molecule using bacterial genetics and physiology methods and then purify the antifungal to try to determine the chemical structure of the antibiotic using a range of chemical and physical methods. We will study how the new antibiotic is assembled in the bacteria that produce it. We have shown that the antifungal antibiotic can also kill simple yeast (fission yeast) in addition to fungi that cause plant disease. The simple yeast is easy to study using genetics and molecular biology methods and so we intend to exploit this by investigating the cellular target of the new antifungal in yeast cells. We expect this information will be also directly relevant to identifying the nature of the molecular target in the plant pathogenic fungi and this will help us in future to develop different natural and semi-synthetic molecules that may protect crop plants from disease and spoilage - and thereby enhance our food security.