Monday, May 2, 2011
Grand Ballroom C-D, 2nd fl (Sheraton Seattle)
The cost-effective production of enzymes frequently depends on overexpression in heterologous hosts. Synthetic genes are increasingly used for enzyme production because sequence information is easier to obtain than the corresponding physical DNA. Protein-coding sequences are commonly re-designed to enhance expression, but there are no experimentally supported design principles. The systematic analysis of gene design parameters shown in this presentation has allowed us to identify codon usage within a gene as a critical determinant of achievable cost-effective protein expression levels in a number of commercially relevant microbial hosts. We propose a biochemical basis for this, as well as design algorithms to ensure high protein production from synthetic genes. Replication of this methodology should allow similar design algorithms to be empirically derived for any enzyme expression system.