AI mining of the bacteriophages metagenome

噬菌体是感染细菌和古菌的病毒，是地球上最常见和最多样化的生物实体，代表着地球上最大的未知遗传物质储藏库。噬菌体可以在所有可想象的生态系统中找到，包括极端的生境(高、低温度、pH和盐度等)。下一代测序(NGS)的发展导致了元基因组数据的爆炸性增长，包括来自大量新型噬菌体的数据。在这个项目中，我们将使用高性能计算来预测我们在Prozomix和Insiligence的合作伙伴提供的整个元基因组数据集的3D结构，以确定在生物经济领域具有潜力的新目标。最初的目标酶家族包括噬菌体编码的裂解酶，内毒素，一组高度多样化的酶，分解细菌(或古生菌)肽多糖层，从而使细胞裂解。内毒素因其在多种条件下具有广泛的活性而成为最有前景的抗菌剂之一，在人类和兽医、农业、生物技术和预防食品生产中的生物被膜等方面都有应用。这些广泛的应用需要特定的酶特性，包括在极端pH、高盐和/或低温条件下的热稳定性和高活性。虽然超高嗜热性的结构特征已经被详细研究，但适应寒冷环境的分子基础仍然难以捉摸。嗜冷酶在生物经济领域备受追捧，因为能够降低生物技术中的反应温度是实现净零目标的关键。特定蛋白质靶标的特征包括生化、生物物理和结构方法。

Bacteriophages, viruses that infect bacteria and archaea, are the most common and most diverse biological entities representing the largest reservoir of unknown genetic material on the planet. Bacteriophages can be found in all conceivable eco-systems including extreme habitats (high and low temperature, pH and salinity etc). The development of next-generation sequencing (NGS) has led to an explosion of metagenomic data including from a plethora of novel bacteriophages. In this project we will employ high-performance computing to predict the 3D structures of entire metagenomics data sets from by our partners at Prozomix and Insiligence to identify novel targets with potential in the bio-economy. The initial target enzyme family comprise phage-encoded lytic enzyme, endolysins, a highly diverse group of enzymes that break down the bacterial (or archaeal) peptidoglycan layer and thus enable cell lysis. Due to their broad activity under a wide range of conditions, endolysins have emerged as one of the most promising antimicrobial agents in application ranging from human and veterinary medicine, agriculture, biotechnology and the prevention of biofilms in food production. These wide-ranging applications require specific enzyme properties, which can include thermostability and high activity in extreme pH, high salt and/or low temperature conditions. While the structural traits of ultra-high thermophilicity have been investigates in a lot of detail, the molecular basis of adaption to cold environments remains elusive. Psychrophilic enzymes are highly sought after in the bio-economy as being able to lower reaction temperatures in biotechnology is key to achieving our net-zero goal. The characterisation of selected protein targets encompasses biochemical, biophysical and structural methods