W0205
Whole Gene Synthesis and High Throughput Crystallography.
Alex B. Burgin, John Walchli, Kathryn Hjerrild, and Lance Stewart,
BioStructures Group, deCODE Genetics, 7869 NE Day Rd W, Bainbridge Island, WA
98110.
Many different bottlenecks must be solved before gene to
structure high throughput crystallography can be an efficient way to solve new
protein structures. One primary bottleneck is rapidly and efficiently creating
gene constructs that are likely to express proteins at high levels and are
likely to provide proteins that can be crystallized. In order to overcome this
bottleneck, we have developed software and associated technology for the design
and synthesis of genes from synthetic oligonucleotides. The process is cost
effective and standardizes the gene construction step thereby dramatically
increasing the number of gene constructs that can be generated in a short period
of time. The resulting genes are codon optimized for a given expression system
thereby increasing the likelihood of obtaining protein in high yield. The
process also allows the precise engineering of protein constructs without
relying upon existing restriction sites or obtaining a cDNA clone.