Lactic acid bacteria: a promising alternative for recombinant protein production

Even though the use of Lactic Acid Bacteria (LAB) is well documented for a variety of dairy food fermentation dating back to the earliest written records [1,2], the use of these Gram-positive anaerobic microorganisms as recombinant microbial cell factories has taken place during the last decades. In this context, it is important to note that the enormous potential of these Generally Recognized As Safe (GRAS) organisms by the US Food and Drug Administration combined with the development of biotechnological, genomic and proteomic tools experienced during last years are expected to convert these microorganisms in emerging platforms for a wide range of applications [2,3]. Nowadays it is widely accepted that LAB-derived products from the industrial manufacture of fermented food such as milk products, vegetables, meat and wine [4,5], as well as lactic acid, antimicrobial peptides and high-value metabolites, are by far the most important LAB applications from an economical point of view. Besides, the use of these organisms as probiotics has also experienced an important increase in the last decades [6-10]. However, it is also important to stress that LAB characteristics make these organisms an ideal bacterial expression system for both homologous and heterologous proteins, including membrane proteins [11]. Interestingly, apart from the cheap and easily scalable protein production associated to the microbial nature of LAB, these species are foodgrade expression hosts, that, contrary to what occurs in Gram-negative bacteria, do not contain endotoxins in their membrane, which are pyrogenic in humans and other mammals [12-14]. In this context, although E. coli is still the first-choice microorganism for the production of heterologous proteins, this species presents several obstacles, including, as mentioned, the presence of endotoxins in its derived products, limiting its final application as cell factory for the production of