TY  - JOUR
A1  - Trösemeier, Jan-Hendrik
A1  - Rudorf, Sophia
A1  - Lößner, Holger
A1  - Hofner, Benjamin
A1  - Reuter, Andreas
A1  - Schulenborg, Thomas
A1  - Koch, Ina
A1  - Bekeredjian-Ding, Isabelle
A1  - Lipowsky, Reinhard
A1  - Kamp, Christel
T1  - Optimizing the dynamics of protein expression
T2  - Scientific reports
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.
KW  - Complexity
KW  - Computational models
KW  - Computational science
KW  - Dynamical systems
KW  - Translation
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50322
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-503227
SN  - 2045-2322
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 9
IS  - 1, Art. 7511
SP  - 1
EP  - 15
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -