4.4 Review

Site-Specific Selenocysteine Incorporation into Proteins by Genetic Engineering

Journal

CHEMBIOCHEM
Volume 22, Issue 20, Pages 2918-2924

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202100124

Keywords

selenocysteine; genetic engineering; selenoprotein

Funding

  1. National Key R&D Program of China [2020YFA0907701, 2019YFA0904103, 2020YFA0908503, 2019YFA0904002]
  2. Sanming Project of Medicine in Shenzhen [SZSM201811092]
  3. SIAT Innovation Program for Excellent Young Researchers

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Selenocysteine is a rare naturally proteinogenic amino acid in living organisms and plays a crucial role in cellular functions. Its incorporation in vivo is highly species-dependent and requires the reprogramming of translation. Many strategies have been developed to overcome the challenges in producing synthetic selenoproteins for understanding their functions.
Selenocysteine (Sec), a rare naturally proteinogenic amino acid, is the major form of essential trace element selenium in living organisms. Selenoproteins, with one or several Sec residues, are found in all three domains of life. Many selenoproteins play a role in critical cellular functions such as maintaining cell redox homeostasis. Sec is usually encoded by an in-frame stop codon UGA in the selenoprotein mRNA, and its incorporation in vivo is highly species-dependent and requires the reprogramming of translation. This mechanistic complexity of selenoprotein synthesis poses a big challenge to produce synthetic selenoproteins. To understand the functions of natural as well as engineered selenoproteins, many strategies have recently been developed to overcome the inherent barrier for recombinant selenoprotein production. In this review, we will describe the progress in selenoprotein production methodology.

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