We are developing a non-automated procedure to rapidly annotate, clone and express the proteins of targeted coding regions from the genome sequence of a novel anaerobic hydrothermal archaeon, OGL-20. Using intelligent bioinformatic strategies, selected open reading frames are identified and used for PCR (Polymerase Chain Reaction) amplification in 96 well configuration. The amplified products are cloned into expression vectors without the use of restriction digest or ligation. Protein expression trials are performed on all clones and those observed to show overexpression are used for large scale protein production. Protein crystallization trials are executed on purified proteins by high throughput screening methods exploring hundreds of crystallization conditions at a time. The overall process will show the ability to efficiently survey the entire hyperthermophilic genome in a cost-effective manner for the production of soluble proteins for crystallographic studies without the use of robotic machinery.