Prototype of a Novel Membrane Protein Expression System for Very Large Scale and Economical Production of Membrane Proteins

78573S The majority of membrane proteins are very difficult to obtain in significant quantities, even at milligram scale, because their natural biosynthesis levels often are very low and currently available protein expression systems are not effective for membrane proteins. The lack of effective method for preparative-scale membrane protein synthesis hampers progress toward a complete understanding of the proteome and prevents the exploitation of available sequences, especially those membrane proteins which constitute the majority of drug targets. This project will develop an in vivo membrane protein expression system for synthesizing any desired protein on a preparative scale, providing recombinant membrane proteins at quantities (grams) comparable to current soluble protein expression systems. Phase I will create prototype(s) for membrane protein expression system by creating genome modifying expression strain(s) to be used with various proprietary membrane protein expression vectors that are currently available. This system will be designed to be very economical, convenient to use, and amenable to high throughput approaches. Commercial Applications and Other Benefits as described by the awardee: The proposed membrane protein expression system should occupy an important niche market where current expression systems are not effective. The system should find use in the large-scale production of medicinally important membrane proteins that are very difficult to prepare. The recombinant membrane proteins could be used in high throughput screening, in structural biology of membrane proteins crucial to structure-based drug design endeavors, and in structural genomics efforts of membrane proteins. Reagents associated with the system could be made available for use by the research community.