Protein
Engineering

ProteinGPS is an engineering technology that can modify proteins for real world applications. A small number of variants are tested using high quality assays representative of the functionality, developability and manufacturability properties that your protein will need. Iterative machine learning and testing steps result in an engineered protein that will work where it matters: the real world.

Real World Performance

High-quality low-throughput assays more precisely mimic the conditions that your protein will experience during its lifecycle. The result is a product that performs better in the real world, from manufacturing to its end-application.

Speed to Market

ATUM's efficient workflow integrates in-house-media, assay, analytical and process development expertise. This accelerates project timelines and positions your protein for fast scale-up and manufacturing.

Intellectual Property

We can help you understand the IP landscape surrounding your protein. This translates to a stronger intellectual property position, giving you freedom to operate and broader patent claims, thereby reducing the risk of product obsolescence and being quickly overtaken by your competitors.

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Bioprospecting for Better Starting Proteins

You want to engineer a protein, but you are not sure about the best starting point? We use phylogenetic analysis to identify, build and test many orthologs of your protein to find variants with better starting properties. Everytime we do this, we identify a preferable starting protein and generate additional data that can be used to find amino acid substitutions encoding functional properties and data to strengthen your intellectual property portfolio.

Homolog

The graph above shows how bioprospecting can pay off. A client asked ATUM to engineer an enzyme for activity against 4 substrates, but their proposed starting point was active against only one of them. We were able to discover several homologs with activity against all 4 substrates.

ProteinGPS® Variant Design Permits Real World Testing

Natural selection guides our ProteinGPS choice of amino acid substitutions.

We begin with a sequence alignment of natural homologs to your protein. Then we score and rank every possible amino acid substitution using several different evolutionary, structural and functional parameters. Finally, we apply Design of Experiment to design protein variants incorporating the highest ranked substitutions. Fewer than 100 variants are needed for each ProteinGPS iteration.

Traditional library screening strategies are time consuming, expensive and inefficient. With millions of variants, you are restricted to using high throughput screens that typically do not accurately measure protein properties under real-world conditions. With fewer than 100 variants, ProteinGPS allows us to use low throughput, high quality assays that mimic the real-world conditions under which you need your protein to perform.

Machine Learning Tells Us Which Amino Acid Changes Affect Each Protein Property

Once the protein properties that are important for the intended application have been measured, ProteinGPS® machine learning is used to determine the effect of each amino acid substitution. The graph below shows the impact of 48 different changes on 3 properties of an industrial enzyme. It is striking that very few changes have a positive effect on activity, thermostability and solubility. This is a severe limitation in traditional library screening approaches. When one property is measured first, and all library members not improved in that dimension are discarded, improvements in other important properties are lost. In contrast, ProteinGPS allows us to identify and combine changes that separately improve solubility, activity and thermostability, resulting in an enzyme that is improved for all three.

Amino Acid Substitution

Pfizer required improved stereospecific activity in an enzyme used for the synthesis of a pharmaceutical intermediary. After 4 rounds of engineering using fewer than 300 variants, the project goals were achieved with over 100-fold improvement in activity.

Have a question?
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ATUM customer support scientists are available to discuss cloning strategies, gene design constraints, bioinformatics analyses, and other molecular biology/biotechnology concerns.

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+1 650 853 8347

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(Basel, Switzerland)
+41 (0) 61 262 0212

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info@atum.bio

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