This invention relates to optimized heterologous production of properly folded and functional proteins. The present invention provides systems and methods involving determination of the optimal mRNA sequence, based on the underlying rates at which codons are translated and folding kinetic of nascent-protein, that maximizes co-translational protein folding of domains in order to maximize the proper folding and quality of the protein produced. The codon translation rates can be determined in a number of ways, including theoretical estimation and, preferably, through experimental data, such as ribosome profiling. The determination of an optimal mRNA sequence through the utilization of codon translation rates under a particular set of conditions allows for application of the method irrespective of the organism from which the protein in question was originally derived.