Advances and Challenges in Cell-Free Incorporation of Unnatural Amino Acids Into Proteins

• Main Authors: Wei Gao, Eunhee Cho, Yingying Liu, Yuan Lu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-05-01
• Series: Frontiers in Pharmacology
• Subjects: cell-free protein synthesis; cell-free synthetic biology; unnatural amino acid; unnatural protein; global suppression; orthogonal translation system
• Online Access: https://www.frontiersin.org/article/10.3389/fphar.2019.00611/full

Incorporation of unnatural amino acids (UNAAs) into proteins currently is an active biological research area for various fundamental and applied science. In this context, cell-free synthetic biology (CFSB) has been developed and recognized as a robust testing and biomanufacturing platform for highly efficient UNAA incorporation. It enables the orchestration of unnatural biological machinery toward an exclusive user-defined objective of unnatural protein synthesis. This review aims to overview the principles of cell-free unnatural protein synthesis (CFUPS) systems, their advantages, different UNAA incorporation approaches, and recent achievements. These have catalyzed cutting-edge research and diverse emerging applications. Especially, present challenges and future trends are focused and discussed. With the development of CFSB and the fusion with other advanced next-generation technologies, CFUPS systems would explicitly deliver their values for biopharmaceutical applications.