Proteins are large, complex molecules made up of a unique sequence of smaller subunits called amino acids. There are 20 different naturally occurring amino acids, each having unique chemical properties, which cause the protein to fold up into distinct three-dimensional structures that define their particular function. A change in just a single amino can greatly affect the function of a protein such as an enzyme or an antibody. It is a cell's genes that contain a specific DNA sequence that dictates the order and type of amino acids that make up each protein made by the cell.
Verenium possesses patented, state-of-the-art gene evolution technologies, called DirectEvolution® platform, that enable the optimization of proteins at the DNA level. Two complementary methods comprise Verenium's DirectEvolution® platform: Gene Site Saturation Mutagenesis™ (GSSM™) and Tunable GeneReassembly™ (TGR™) technologies.
Verenium’s suite of DirectEvolution® technologies provides potentially significant competitive advantages, including the ability to generate the broadest amount of genetic sequence diversity, the ability to make fine changes across an entire gene, and the freedom to use unrelated genes when recombining starting genes. Additionally, both GSSM™ and TGR™ technologies are able to modify codons to achieve increased protein expression for manufacturing without changing the fundamental amino acid sequence.
GSSM™ technology creates a family of related proteins that all differ from a parent protein by at least a single amino acid change at any defined position or at each position along the protein sequence. GSSM™ technology can produce all possible single amino acid substitutions at every position within a protein sequence, removing the need for prior knowledge about the protein structure and 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. The GSSM™ library can be screened for novel enzymes with characteristics such as increased ability to function at high temperature or a targeted pH range, increased reaction rate or resistance to deactivating chemicals. More >>
Beneficial mutations identified from a GSSM™ screen can then be combined in a combinatorial fashion using the GeneReassembly™ process to create a superior version of the parental protein. GeneReassembly™ technology allows blending of gene sequences independent of sequence homology. Multiple variations can be introduced at precise positions within the genes. The complexity of the variant library can be fine-tuned by the number of parental genes used and the average number of variations used in the reaction. Moreover, the number of variations can be modulated to reflect the resilience of the targeted gene family to mutations. In addition, any structural information available can be incorporated into the sequence design, and codon usage can be optimized during the reassembly process to maximize expression in the selected production host. Verenium’s GeneReassembly™ method represents the next generation of gene-blending evolution methods.
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