Arginine deiminase: recent advances in discovery, crystal structure, and protein engineering for improved properties as an anti-tumor drug

作者：Han Rui Zhi; Xu Guo Chao; Dong Jin Jun; Ni Ye

来源：Applied Microbiology and Biotechnology, 2016, 100(11): 4747-4760.

DOI：10.1007/s00253-016-7490-z

• Arginine deiminase (ADI)
• Protein engineering
• Directed evolution
• PEGylation
• Anti-tumor

Arginine deiminase (ADI) is an important arginine-degrading enzyme with wide applications, in particular as an anti-cancer agent for the therapy of arginine-auxotrophic tumors. In recent years, novel ADIs with excellent properties have been identified from various organisms, and crystal structures of ADI were investigated. To satisfy the requirements of potential therapeutic applications, protein engineering has been performed to improve the activity and properties of ADIs. In this mini-review, we systematically summarized the latest progress on identification and crystal structure of ADIs, and protein engineering strategies for improved enzymatic properties, such as pH optimum, K (m) and k (cat) values, and thermostability. We also outlined the PEGylation of ADI for improved circulating half-life and immunogenicity, as well as their performance in clinical trials. Finally, perspectives on extracellular secretion and property improvement of ADI were discussed.

• 出版日期2016-6
• 单位江南大学