Heterologous Protein Secretion from Yeast

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Abstract
Secretion of calf prochymosin from yeast yields fully activable zymogen while production in the yeast cytoplasm yields insoluble, unactivable enzyme with aberrant disulfide bonding. Factors that increase the efficiency of secretion of prochymosin from yeast are use of a yeast secretion signal sequence, integration of the transcriptional unit into the yeast genome, and specific mutations in a number of host cell genes. In combination, these factors increase the secretion of calf prochymosin from less than 1 percent to more than 80 percent of the amount produced. Host mutations that increase prochymosin secretion also increase bovine growth hormone secretion more than 15-fold. These discoveries may be generally useful for production of many secreted mammalian proteins made inside microorganisms as insoluble aggregates.