Wang Hui, Wang Qian, Liu Yuqian, Liao Xiaoping, Chu Huanyu, Chang Hong, Cao Yang, Li Zhigang, Zhang Tongcun, Cheng Jian, Jiang Huifeng
College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
Synth Syst Biotechnol. 2021 Apr 24;6(2):102-109. doi: 10.1016/j.synbio.2021.04.004. eCollection 2021 Jun.
Plant cytochrome P450s play key roles in the diversification and functional modification of plant natural products. Although over 200,000 plant P450 gene sequences have been recorded, only seven crystalized P450 genes severely hampered the functional characterization, gene mining and engineering of important P450s. Here, we combined Rosetta homologous modeling and MD-based refinement to construct a high-resolution P450 structure prediction process (PCPCM), which was applied to 181 plant P450s with identified functions. Furthermore, we constructed a ligand docking process (PCPLD) that can be applied for plant P450s virtual screening. 10 examples of virtual screening indicated the process can reduce about 80% screening space for next experimental verification. Finally, we constructed a plant P450 database (PCPD: http://p450.biodesign.ac.cn/), which includes the sequences, structures and functions of the 181 plant P450s, and a web service based on PCPCM and PCPLD. Our study not only developed methods for the P450-specific structure analysis, but also introduced a universal approach that can assist the mining and functional analysis of P450 enzymes.
植物细胞色素P450在植物天然产物的多样化和功能修饰中发挥着关键作用。尽管已记录了超过20万个植物P450基因序列，但仅有7个结晶的P450基因严重阻碍了重要P450的功能表征、基因挖掘和工程改造。在此，我们结合了Rosetta同源建模和基于分子动力学的优化，构建了一个高分辨率的P450结构预测流程（PCPCM），并将其应用于181个已确定功能的植物P450。此外，我们构建了一个可用于植物P450虚拟筛选的配体对接流程（PCPLD）。10个虚拟筛选实例表明，该流程可为后续实验验证减少约80%的筛选空间。最后，我们构建了一个植物P450数据库（PCPD：http://p450.biodesign.ac.cn/），其中包括181个植物P450的序列、结构和功能，以及一个基于PCPCM和PCPLD的网络服务。我们的研究不仅开发了针对P450的结构分析方法，还引入了一种可辅助P450酶挖掘和功能分析的通用方法。
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