MOSAIC: Codon Harmonization of Monte Carlo-Based Simulated Annealing for Linked Codons in Heterologous Protein Expression

Fuente: arXiv
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Auteurs principaux: Jeong, Yoonho, Yang, Chengcheng, Hariri, Ryan Fernandez Medina, Kim, Jihoo, Lee, Eok Kyun, Lee, Younghoon, Kim, Won June, Lee, Seung Seo, Choi, Insung S.
Format: Preprint
Publié: 2025
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author Jeong, Yoonho
Yang, Chengcheng
Hariri, Ryan Fernandez Medina
Kim, Jihoo
Lee, Eok Kyun
Lee, Younghoon
Kim, Won June
Lee, Seung Seo
Choi, Insung S.
author_facet Jeong, Yoonho
Yang, Chengcheng
Hariri, Ryan Fernandez Medina
Kim, Jihoo
Lee, Eok Kyun
Lee, Younghoon
Kim, Won June
Lee, Seung Seo
Choi, Insung S.
contents Codon usage bias has a crucial impact on the translation efficiency and co-translational folding of proteins, necessitating the algorithmic development of codon optimization/harmonization methods, particularly for heterologous recombinant protein expression. Codon harmonization is especially valuable for proteins sensitive to translation rates, because it can potentially replicate native translation speeds, preserving proper folding and maintaining protein activity. This work proposes a Monte Carlo-based codon harmonization algorithm, MOSAIC (Monte Carlo-based Simulated Annealing for Linked Codons), for the harmonization of a set of linked codons, which differs from conventional codon harmonization, by focusing on the codon sets rather than individual ones. Our MOSAIC demonstrates robust computational performance on ribosomal proteins (S18, S15, S10, and L11) as model systems. Among them, the harmonized gene of RP S18 was expressed and compared with the expression of the wild-type gene. The harmonized gene clearly yielded a larger quantity of the protein, from which the amount of the soluble protein was also significant. These results underscored the potential of the linked codon harmonization approach to enhance the expression and functionality of sensitive proteins, setting the stage for more efficient production of recombinant proteins in various biotechnological and pharmaceutical applications.
format Preprint
id arxiv_https___arxiv_org_abs_2511_10708
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle MOSAIC: Codon Harmonization of Monte Carlo-Based Simulated Annealing for Linked Codons in Heterologous Protein Expression
Jeong, Yoonho
Yang, Chengcheng
Hariri, Ryan Fernandez Medina
Kim, Jihoo
Lee, Eok Kyun
Lee, Younghoon
Kim, Won June
Lee, Seung Seo
Choi, Insung S.
Quantitative Methods
Codon usage bias has a crucial impact on the translation efficiency and co-translational folding of proteins, necessitating the algorithmic development of codon optimization/harmonization methods, particularly for heterologous recombinant protein expression. Codon harmonization is especially valuable for proteins sensitive to translation rates, because it can potentially replicate native translation speeds, preserving proper folding and maintaining protein activity. This work proposes a Monte Carlo-based codon harmonization algorithm, MOSAIC (Monte Carlo-based Simulated Annealing for Linked Codons), for the harmonization of a set of linked codons, which differs from conventional codon harmonization, by focusing on the codon sets rather than individual ones. Our MOSAIC demonstrates robust computational performance on ribosomal proteins (S18, S15, S10, and L11) as model systems. Among them, the harmonized gene of RP S18 was expressed and compared with the expression of the wild-type gene. The harmonized gene clearly yielded a larger quantity of the protein, from which the amount of the soluble protein was also significant. These results underscored the potential of the linked codon harmonization approach to enhance the expression and functionality of sensitive proteins, setting the stage for more efficient production of recombinant proteins in various biotechnological and pharmaceutical applications.
title MOSAIC: Codon Harmonization of Monte Carlo-Based Simulated Annealing for Linked Codons in Heterologous Protein Expression
topic Quantitative Methods
url https://arxiv.org/abs/2511.10708