Microbial synthesis of high-molecular-weight, highly repetitive protein polymers

Juya Jeon, Washington University in St. Louis
Shri Venkatesh Subramani, Washington University in St. Louis
Kok Zhi Lee, Washington University in St. Louis
Bojing Jiang, Washington University in St. Louis
Fuzhong Zhang, Washington University School of Medicine in St. Louis


High molecular weight (MW), highly repetitive protein polymers are attractive candidates to replace petroleum-derived materials as these protein-based materials (PBMs) are renewable, biodegradable, and have outstanding mechanical properties. However, their high MW and highly repetitive sequence features make them difficult to synthesize in fast-growing microbial cells in sufficient amounts for real applications. To overcome this challenge, various methods were developed to synthesize repetitive PBMs. Here, we review recent strategies in the construction of repetitive genes, expression of repetitive proteins from circular mRNAs, and synthesis of repetitive proteins by ligation and protein polymerization. We discuss the advantages and limitations of each method and highlight future directions that will lead to scalable production of highly repetitive PBMs for a wide range of applications.