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Who We Are
proteolutions is a Berlin-based biotech / bioinformatics service provider. We have developed a pioneering gene optimization algorithm that increases soluble protein yields in heterologous expression hosts far beyond the current state of the art. Unfavorable sequences are systematically avoided through our holistic approach that learns the optimal sequence neighborhoods from transcriptomic data and explores a large parameter space. Our optimized sequences will convey the highest reliability and best possible yields to your protein production endeavors in any host and at any scale.
One key parameter of all protein expression systems is the input DNA sequence, decisive for protein production, fold, solubility and lastly, high protein yields. Because of the combinatorial nature of codons, there is a plethora of possible sequences to choose from, even for relatively small proteins. For example, the redundancy of the genetic code allows for about 10200 different DNA sequences that can be synthesized to encode the human 387 amino acid protease pepsin. All of these sequences will yield different amounts of soluble target protein in given expression hosts. So it is a true challenge to find the optimal sequence for your target gene. See our Solutions overview for more information.
Our Method
To date, a multitude of strategies are available to locally adapt codon choices to the expression host's preferences, for example simple codon optimization, the codon adaptation index or the codon context. Analyzing these protocols, we find that despite an improvement compared to unoptimized sequences, they tend to be generally unreliable since they are restricted to local events in the gene sequence, disregarding connectivity – and this can have undesirable effects during gene expression.
We at proteolutions have extensively tested our DNA optimization algorithm and the principle of codon connectivity. With the examples below we show that soluble gene expression directly increases with the strength of codon connectivity applied to the optimization and that our DNA optimization principle is universially applicable from bacterial up to mammalian hosts.
Expression of a hydrolase in E. coli
The soluble protein yields of this hydrolase are typically low when using state of the art codon optimization. Here we investigated the effect of the proteolutions optimization approach with two different settings (codon connectivity over a medium or wide codon range). Even a standard implementation of our codon optimization (over a medium codon range) is superior to the state of the art and the soluble protein yields increase with a wider codon connectivity.
Expression of a deaminase in E. coli
Some proteins like this deaminase from Arabidopsis are hard to express in a soluble form. Even when using a state-of-the-art codon optimized gene, many liters of E. coli cell culture are required to obtain only trace amounts of protein. Here, our optimization strategy increased soluble protein yields nearly by a factor of three, drastically reducing the efforts required to get soluble and functional protein.
Expressions in mammalian cells
Although human cell culture is a very robust expression system, gene optimization often leads to failed expressions or low expression rates. In these three cases tested in HeLa and HEK293 cells, proteolutions gene optimization not only yields superior soluble protein amounts, but also the ratio of fluorescing (functionally folded) protein in the case of Citrin is substantially higher.
The History of proteolutions
2017
Concept
proteolutions co-founders realize a large potential for the improvement of synthetic DNA sequences for protein expression and unite their biochemical knowledge, protein expression experience in various hosts (human, insect, E. coli…) and informatic skills.
2018
Development
The first proteolutions algorithm is in place, exploring a large parameter space, optimizing sequences with a metaheuristic approximation procedure and implementing a holistic view of connectivities within a gene.
2020
Founding
Based on the superior DNA sequence optimization capacities, proteolutions is founded in 2020 as a biotech / bioinformatics start-up.
2021
Refinement
The proteolutions algorithm is further optimized and enables soluble expression of very difficult targets, and also increases soluble protein yields by up to seven-fold, compared with state-of-the-art protocols currently in place.
2022
IP
The first proteolutions patent filed covering the entire gene optimization procedure and several successful applications of the algorithm compared to the state-of-the-art.
2024
Application
Several very positive testimonials from colleagues in the protein expression field, who tested proteolutions sequences.
2025
Activation
proteolutions goes online to provide a reliable and robust on-demand service for gene optimization.
User Stories
© 2025
“proteolutions” is a registered trademark of Proteolutions UG (haftungsbeschränkt) in Germany and the EU.