Use of Streptomyces as a host for the production of heterologous proteins

Abstract

The commercial production of proteins in recombinant microorganisms for therapeutic use is of substantial interest. Several microbial systems have been developed so far, but when the microbial expression of recombinant proteins is discussed, Escherichia coli is usually assumed to be the host organism. However, in these bacteria, expressed proteins remain in the periplasm and often precipitate as inclusion bodies, which may seriously complicate downstream processing. Faced with this problem, several genders of Gram-positive bacteria are being tested as host for the production of heterologous proteins due to their ability to secrete proteins in the culture medium. Among them is Streptomyces, since several of their species are known to secrete proteins in high amounts. Due to the absence of an extensive restrictionmodification system, limited protease activity and the availability of suitable vector systems, Streptomyces lividans is the host of choice for the secretory production of heterologous proteins. Therefore, it is of considerable interest to improve Streptomyces lividans as a bacterial host for obtaining homologous and several heterologous proteins with remarkable efficiency. In this article, it is reviewed the current knowledge on the molecular elements and factors that affect the expression and secretion of proteins, the optimization of fermentation conditions and the main studies made when Streptomyces lividans was used as host. It was concluded that at present there is not possible to stablish a general rule for the expression and secretion of recombinant proteins in Streptomyces because each one need before a basic research about molecular elements and factors that affect exoression and secretion of proteins.