Mechanisms Affecting the Biosynthesis and Incorporation Rate of Selenocysteine

Peng, Jing-Jing; Yue, Shi-Yang; Fang, Yu‐Hui; Liu, Xiaoling; Wang, Cheng-Hua

doi:10.3390/molecules26237120

Cited by 11 publications

(5 citation statements)

References 70 publications

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“…It is well known that there is additional information in the coding sequence of a gene beyond the genetic code for translating nucleotide triplets (codons). For example, the UGA stop codon is translated to selenocysteine if a so-called SECIS pattern is present 52 , 53 . There is also a process termed programmed ribosomal frameshifting by which the ribosome shifts the reading frame by one or two nucleotides in either the + or the − direction 54 .…”

Section: Resultsmentioning

confidence: 99%

Design of typical genes for heterologous gene expression

Simm

Popova

Braus

et al. 2022

Sci Rep

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Heterologous protein expression is an important method for analysing cellular functions of proteins, in genetic circuit engineering and in overexpressing proteins for biopharmaceutical applications and structural biology research. The degeneracy of the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, plays an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the influence of a profiled codon usage adaptation approach on protein expression levels in the eukaryotic model organism Saccharomyces cerevisiae. We selected green fluorescent protein (GFP) and human α-synuclein (αSyn) as representatives for stable and intrinsically disordered proteins and representing a benchmark and a challenging test case. A new approach was implemented to design typical genes resembling the codon usage of any subset of endogenous genes. Using this approach, synthetic genes for GFP and αSyn were generated, heterologously expressed and evaluated in yeast. We demonstrate that GFP is expressed at high levels, and that the toxic αSyn can be adapted to endogenous, low-level expression. The new software is publicly available as a web-application for performing host-specific protein adaptations to a set of the most commonly used model organisms (https://odysseus.motorprotein.de).

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Section: Resultsmentioning

confidence: 99%

Design of typical genes for heterologous gene expression

Simm

Popova

Braus

et al. 2022

Sci Rep

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“…Two partially conserved yet distinct mechanisms for Sec incorporation into proteins evolved in bacteria as compared to archaea and eukaryotes ( Figure 2 ). In both mechanisms, the meaning of selected UGA stop codons is converted from a stop to a sense codon that encodes Sec [ 15 , 16 , 17 ]. In all Sec-decoding organisms, Sec is synthesized from serine (Ser) on its cognate tRNA (tRNA Sec ).…”

Section: A Natural Expansion Of the Genetic Code With Selenocysteinementioning

confidence: 99%

Biosynthesis, Engineering, and Delivery of Selenoproteins

Wright,

O’Donoghue

2023

IJMS

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Selenocysteine (Sec) was discovered as the 21st genetically encoded amino acid. In nature, site-directed incorporation of Sec into proteins requires specialized biosynthesis and recoding machinery that evolved distinctly in bacteria compared to archaea and eukaryotes. Many organisms, including higher plants and most fungi, lack the Sec-decoding trait. We review the discovery of Sec and its role in redox enzymes that are essential to human health and important targets in disease. We highlight recent genetic code expansion efforts to engineer site-directed incorporation of Sec in bacteria and yeast. We also review methods to produce selenoproteins with 21 or more amino acids and approaches to delivering recombinant selenoproteins to mammalian cells as new applications for selenoproteins in synthetic biology.

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“…Selenocysteine (Sec), differs from cysteine (Cys) by a single atom, selenium replacing sulfur (Figure 1). Selenium incorporation into Sec is a highly complex process, owing to the complex genetic machinery required for both the synthesis of Sec-specific tRNA, and the co-translational use of the codon "UGA", which also functions as the stop codon [14,15]. The biosynthesis of Sec is significantly more complicated than the other proteinogenic amino acids, including Cys [16].…”

Section: The Role Of Elemental Selenium In Selenoproteinsmentioning

confidence: 99%

The Selenoprotein Glutathione Peroxidase 4: From Molecular Mechanisms to Novel Therapeutic Opportunities

Weaver¹,

Skouta²

2022

Preprint

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The selenoprotein glutathione peroxidase 4 (GPX4) is one of the main antioxidant mediators in the human body. Its central function involves the reduction of complex hydroperoxides into their respective alcohols often using reduced Glutathione (GSH) as a reducing agent. GPX4 has become a hotspot therapeutic target in biomedical research following its characterization as a chief regulator of ferroptosis, and its subsequent recognition as a specific pharmacological target for the treatment of an extensive variety of human diseases including cancers and neurodegenerative disorders. Several recent studies have provided insights into how GPX4 is distinguished from the rest of the glutathione peroxidase family, the unique biochemical properties of GPX4, how GPX4 is related to lipid peroxidation and ferroptosis, and how the enzyme may be modulated as a potential therapeutic target. This current report aims to review the literature underlying all these insights and present an up-to-date perspective on the current understanding of GPX4 as a potential therapeutic target.

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Mechanisms Affecting the Biosynthesis and Incorporation Rate of Selenocysteine

Cited by 11 publications

References 70 publications

Design of typical genes for heterologous gene expression

Design of typical genes for heterologous gene expression

Biosynthesis, Engineering, and Delivery of Selenoproteins

The Selenoprotein Glutathione Peroxidase 4: From Molecular Mechanisms to Novel Therapeutic Opportunities

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