Laboratory of Applied Biotechnology, Department of Biotechnology, Ghent University, 9000 Gent, Belgium.
BIOBIX, Department of Data Analysis and Mathematical Modelling, Ghent University, 9000 Gent, Belgium.
Viruses. 2021 Jun 26;13(7):1240. doi: 10.3390/v13071240.
Phage lytic proteins are a clinically advanced class of novel enzyme-based antibiotics, so-called enzybiotics. A growing community of researchers develops phage lytic proteins with the perspective of their use as enzybiotics. A successful translation of enzybiotics to the market requires well-considered selections of phage lytic proteins in early research stages. Here, we introduce PhaLP, a database of phage lytic proteins, which serves as an open portal to facilitate the development of phage lytic proteins. PhaLP is a comprehensive, easily accessible and automatically updated database (currently 16,095 entries). Capitalizing on the rich content of PhaLP, we have mapped the high diversity of natural phage lytic proteins and conducted analyses at three levels to gain insight in their host-specific evolution. First, we provide an overview of the modular diversity. Secondly, datamining and interpretable machine learning approaches were adopted to reveal host-specific design rules for domain architectures in endolysins. Lastly, the evolution of phage lytic proteins on the protein sequence level was explored, revealing host-specific clusters. In sum, PhaLP can act as a starting point for the broad community of enzybiotic researchers, while the steadily improving evolutionary insights will serve as a natural inspiration for protein engineers.
噬菌体裂解蛋白是一类临床先进的新型酶基抗生素，即所谓的酶抗生素。越来越多的研究人员开发噬菌体裂解蛋白，并期望将其作为酶抗生素推向市场。要成功地将酶抗生素转化为市场产品，需要在早期研究阶段就经过深思熟虑地选择噬菌体裂解蛋白。在这里，我们介绍了 PhaLP，这是一个噬菌体裂解蛋白数据库，它作为一个开放的门户，为噬菌体裂解蛋白的开发提供了便利。PhaLP 是一个全面的、易于访问的、自动更新的数据库（目前有 16095 条记录）。利用 PhaLP 丰富的内容，我们绘制了天然噬菌体裂解蛋白的高度多样性图谱，并在三个层面上进行了分析，以深入了解其宿主特异性进化。首先，我们提供了一个模块多样性的概述。其次，采用数据挖掘和可解释的机器学习方法，揭示了内切酶结构域中宿主特异性设计规则。最后，探索了噬菌体裂解蛋白在蛋白质序列水平上的进化，揭示了宿主特异性聚类。总之，PhaLP 可以作为广大酶抗生素研究人员的起点，而不断提高的进化见解将为蛋白质工程师提供自然的灵感。
