R&D : Advancing Enzyme Technology : Optimization

DirectEvolution® Technology

Developing High-Performance Proteins with Industry-Leading Gene Evolution Technologies

Proteins are naturally occurring, complex molecules made up of long chains of individually linked amino acids. Found everywhere in nature are 20 different amino acids, each having distinctive chemical properties. Protein amino acid sequences are directly translated from a gene DNA blueprint, and the unique sequence of amino acids of each resulting protein directs it to take on a specific form and function. A change in just one amino acid can greatly affect the function and properties of a protein such as an enzyme or an antibody. As you might imagine, enabling technologies are needed to harness the potential compounding diversity of 20 possibilities at each site in typical proteins of hundreds of amino acids.

State-of-the-art gene evolution technologies

Verenium possesses patented, state-of-the-art gene evolution technologies that make possible optimization of proteins at the DNA level. Verenium’s suite of DirectEvolution^® technologies provides significant competitive advantages, including the most comprehensive and non-biased gene evolution platform, the ability to make fine changes across an entire gene and the freedom to reassemble the widest variety of genes with ultimate precision.

Our technologies are able to modify gene sequences to achieve not only increased protein activity and stability, but also other desirable qualities such as increased expression for manufacturing without changing the fundamental amino acid sequence.

Two complementary methods lie beneath Verenium’s
DirectEvolution^® platform:

Gene Site Saturation Mutagenesis™ (GSSM™) Technology

Verenium’s patented GSSM™ technology rapidly generates protein variants by incorporating any or all of the 20 possible amino acids at every position along a protein’s sequence allowing all possibilities to be tested in an unbiased manner. The library of variants created using GSSM™ technology is then available to be expressed and screened for improved properties. From our experience, often just a few amino acid changes can result in proteins with significantly improved characteristics such as temperature stability, pH stability, increased reaction rate or resistance to deactivating chemicals.

Tunable GeneReassembly™ (TGR™) Technology

Verenium uses Tunable GeneReassembly™ technology to optimize the characteristics of proteins by combining the best properties of candidate genes into a new, high performance molecule. Flexible but exacting design is at the heart of TGR™ which, in addition to sequence information, can incorporate supplementary knowledge such as 3-D structural information and codon optimization. GeneReassembly™ technology allows blending of gene sequences at precise positions, enabling us to create complete combinatorial libraries of all favorable variants from GSSM™ as well as reassembled genes from the most useful members of an entire protein family. As such, TGR™ technology is an excellent complement to GSSM™ and significantly increases the success of finding gene products that will lead to novel and next generation enzymes.