Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | 7511 |
| Seitenumfang | 15 |
| Fachzeitschrift | Scientific reports |
| Jahrgang | 9 |
| Ausgabenummer | 1 |
| Publikationsstatus | Veröffentlicht - 17 Mai 2019 |
| Extern publiziert | Ja |
Abstract
Heterologously expressed genes require adaptation to the host organism to ensure adequate levels of protein synthesis, which is typically approached by replacing codons by the target organism’s preferred codons. In view of frequently encountered suboptimal outcomes we introduce the codon-specific elongation model (COSEM) as an alternative concept. COSEM simulates ribosome dynamics during mRNA translation and informs about protein synthesis rates per mRNA in an organism- and context-dependent way. Protein synthesis rates from COSEM are integrated with further relevant covariates such as translation accuracy into a protein expression score that we use for codon optimization. The scoring algorithm further enables fine-tuning of protein expression including deoptimization and is implemented in the software OCTOPOS. The protein expression score produces competitive predictions on proteomic data from prokaryotic, eukaryotic, and human expression systems. In addition, we optimized and tested heterologous expression of manA and ova genes in Salmonella enterica serovar Typhimurium. Superiority over standard methodology was demonstrated by a threefold increase in protein yield compared to wildtype and commercially optimized sequences.
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in: Scientific reports, Jahrgang 9, Nr. 1, 7511, 17.05.2019.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Optimizing the dynamics of protein expression
AU - Trösemeier, Jan-Hendrik
AU - Rudorf, Sophia
AU - Loessner, Holger
AU - Hofner, Benjamin
AU - Reuter, Andreas
AU - Schulenborg, Thomas
AU - Koch, Ina
AU - Bekeredjian-Ding, Isabelle
AU - Lipowsky, Reinhard
AU - Kamp, Christel
N1 - Publisher Copyright: © 2019, The Author(s).
PY - 2019/5/17
Y1 - 2019/5/17
N2 - Heterologously expressed genes require adaptation to the host organism to ensure adequate levels of protein synthesis, which is typically approached by replacing codons by the target organism’s preferred codons. In view of frequently encountered suboptimal outcomes we introduce the codon-specific elongation model (COSEM) as an alternative concept. COSEM simulates ribosome dynamics during mRNA translation and informs about protein synthesis rates per mRNA in an organism- and context-dependent way. Protein synthesis rates from COSEM are integrated with further relevant covariates such as translation accuracy into a protein expression score that we use for codon optimization. The scoring algorithm further enables fine-tuning of protein expression including deoptimization and is implemented in the software OCTOPOS. The protein expression score produces competitive predictions on proteomic data from prokaryotic, eukaryotic, and human expression systems. In addition, we optimized and tested heterologous expression of manA and ova genes in Salmonella enterica serovar Typhimurium. Superiority over standard methodology was demonstrated by a threefold increase in protein yield compared to wildtype and commercially optimized sequences.
AB - Heterologously expressed genes require adaptation to the host organism to ensure adequate levels of protein synthesis, which is typically approached by replacing codons by the target organism’s preferred codons. In view of frequently encountered suboptimal outcomes we introduce the codon-specific elongation model (COSEM) as an alternative concept. COSEM simulates ribosome dynamics during mRNA translation and informs about protein synthesis rates per mRNA in an organism- and context-dependent way. Protein synthesis rates from COSEM are integrated with further relevant covariates such as translation accuracy into a protein expression score that we use for codon optimization. The scoring algorithm further enables fine-tuning of protein expression including deoptimization and is implemented in the software OCTOPOS. The protein expression score produces competitive predictions on proteomic data from prokaryotic, eukaryotic, and human expression systems. In addition, we optimized and tested heterologous expression of manA and ova genes in Salmonella enterica serovar Typhimurium. Superiority over standard methodology was demonstrated by a threefold increase in protein yield compared to wildtype and commercially optimized sequences.
UR - http://www.scopus.com/inward/record.url?scp=85065845767&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-43857-5
DO - 10.1038/s41598-019-43857-5
M3 - Article
VL - 9
JO - Scientific reports
JF - Scientific reports
SN - 2045-2322
IS - 1
M1 - 7511
ER -