Industrial production of heterologous proteins by fed-batch cultures of the yeastSaccharomyces cereuisiae

Abstract

This review concerns the issues involved in the industrial development of fed-batch culture processes with Saccharomyces cerevisiae strains producing heterologous proteins. Most of process development considerations with fed-batch recombinant cultures are linked to the reliability and reproducibility of the process for manufacturing environments where quality assurance and quality control aspects are paramount. In this respect, the quality, safety and efficacy of complex biologically active molecules produced by recombinant techniques are strongly influenced by the genetic background of the host strain, genetic stability of the transformed strain and production process factors. An overview of the recent literature of these culture-related factors is coupled with our experience in yeast fed-batch process development for producing various therapeutic grade proteins. The discussion is based around three principal topics: genetics, microbial physiology and fed-batch process design. It includes the fundamental aspects of yeast strain physiology, the nature of the recombinant product, quality control aspects of the biological product, features of yeast expression vectors, expression and localization of recombinant products in transformed cells and fed-batch process considerations for the industrial production of Saccharomyces cerevisiae recombinant proteins. It is our purpose that this review will provide a comprehensive understanding of the fed-batch recombinant production processes and challenges commonly encountered during process development.

Industrial Relevance of Chromosomal Copy Number Variation in Saccharomyces Yeasts

“…Saccharomyces yeasts are applied in a large and expanding number of industrial processes (1), ranging from traditional applications such as dough leavening (2) and beer (3) and wine fermentation (4) to modern processes such as the production of first- and second-generation fuel ethanol (5, 6), other low-molecular-weight compounds (7), and heterologous proteins (8). Selection and improvement of yeast strains remain essential to meet the complex, diverse, and continually changing performance criteria for industrial applications of Saccharomyces yeasts (9).…”

Performance of the auxotrophic Saccharomyces cerevisiae BY4741 as host for the production of IL-1β in aerated fed-batch reactor: role of ACA supplementation, strain viability, and maintenance energy

“…Indeed, sugar limitation avoids over-flow metabolism and favors oxidative metabolism with high yield of biomass and recombinant product [16]. …”

Strategies for improving production and purification of a recombinant protein: rP30 of Toxoplasma gondii expressed in the yeast Schizosaccharomyces pombe

“…Taking into account successive optimizations of the synthetic medium for yeast introduced by Fiechter et al [41] and modified by Mendoza et al [42] concerning the addition of casein hydrolysate as organic nitrogen, the influence of the source of nitrogen was explored. The addition of 10 g l −1 of a complex nitrogen source obtained from chemical or enzymatic hydrolysate of casein and yeast extract brings a gain in growth rate, and consequently in the biomass and expression of rP30 especially for the bio-Trypcase and the yeast extract.…”