Abstract
Lactococcus lactis has progressed a long way since its discovery and initial use in dairy product fermentation, to its present biotechnological applications in genetic engineering for the production of various recombinant proteins and metabolites that transcends the heterologous species barrier. Key desirable features of this gram-positive lactic acid non-colonizing gut bacteria include its generally recognized as safe (GRAS) status, probiotic properties, the absence of inclusion bodies and endotoxins, surface display and extracellular secretion technology, and a diverse selection of cloning and inducible expression vectors. This have made L. lactis a desirable and promising host on par with other well established model bacterial or yeast systems such as Escherichia coli, Salmonella cerevisiae and Bacillus subtilis. In this article, we review recent technological advancements, challenges, future prospects and current diversified examples on the use of L. lactis as a microbial cell factory. Additionally, we will also highlight latest medical-based applications involving whole-cell L. lactis as a live delivery vector for the administration of therapeutics against both communicable and non-communicable diseases.
Highlights
Despite the common association of Lactococcus lactis with dairy products, the bacterium was originally isolated from plants where it was believed to be dormant, and only became active and multiplied in the gastrointestinal tract after being consumed by ruminants [1]
It is classified as a gram-positive, spherical, homolactate, non-sporulating, and facultative anaerobic gut bacteria with hundreds of strains and biovariants published to date [3, 4]
Over the past two decades, L. lactis has been proven to be an excellent host for the expression of membrane proteins due to several advantages: (i) they are amino acid auxotrophs allowing incorporation of labels for detection, (ii) they only have a single membrane layer compared to E. coli, (iii) they have a small genome size with little proteolytic activity, and (iv) they come with extensive genetic engineering tools including the highly efficient and well tested nisin controlled gene expression (NICE) system
Summary
Despite the common association of Lactococcus lactis with dairy products, the bacterium was originally isolated from plants where it was believed to be dormant, and only became active and multiplied in the gastrointestinal tract after being consumed by ruminants [1]. Successful examples include murine IL-12 [81], Table 2 Recombinant therapeutics produced from various Lactococcus lactis strains
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