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Lactococcus lactis is a food-grade, and generally recognized as safe, bacterium, which making it ideal for producing plasmid DNA (pDNA) or recombinant proteins for industrial or pharmaceutical applications. A paper published in Microorganisms by Sofia Duarte and Gabriel Monteiro from BERG-iBB reviews the major findings from L. lactis transcriptome and proteome studies, with an overexpression of native or recombinant proteins. These studies provide important insights on how to engineer the plasmid vectors and/or the strains in order to achieve high pDNA or recombinant proteins yields, with high quality standards. 

BERG-iBB researchers led by Gabriel Monteiro are engineering lactic acid bacteria and plasmid vectors in order to develop a flexible platform for biomolecule production. The cover image of the August issue of Biotechnology Journal highlights a recent contribution of the group. The work is part of the FCT-funded project LactoSynt.

While Lactococcus lactis is traditionally associated with the fermented food industry, applications of these bacteria have been spreading to the pharmaceutical industry. The goal is to use L. lactis as cell factories for the production of added-value recombinant proteins and plasmid DNA (pDNA) for DNA vaccination, as a safer and industrially profitable alternative to the traditional Escherichia coli host. In a recent review in International Molecular Sciences, Sofia Duarte and Gabriel Monteiro from BERG-iBB critically systematize the plasmid replicons available for the production of pharmaceutical-grade pDNA and recombinant proteins by L. lactis. The work is funded by the LactoSynt project.

The lipopolysaccharide-free Lactococcus lactis is an interesting alternative to E. coli for plasmid production. A key requirement for L. lactis‐based plasmid manufacturing is the availability of high‐copy number plasmids. In a recent publication in Biotechnology Journal, BERG-iBB researchers led by Gabriel Monteiro describe how engineering of the repDE Ribosome Binding Site led to an increase in the copy number  of plasmid pTRKH3 in L. lactis LMG19460 cells.  The number of copies of mutant pTRKH3‐b increased up to 215 copies per chromosome, which corresponds to a 3.5 fold increase when compared to the non‐modified pTRKH3. The new mutant is an important step towards the establishment of lactic acid bacteria as viable plasmid producers. The work was developed in the context of the FCT-funded, LactoSynt project.

The project "LactoSynt: Lactic Acid Bacteria as Cell Factories: a Synthetic Biology Approach for Plasmid DNA and Recombinant Protein Production" has been recommended for funding by FCT (2017 Call for SR&TD Project Grants). The goal of LactoSynt is to engineer lactic acid bacteria and plasmid vectors in order to develop a flexible platform for biomolecule production. Applications in the pharmaceutical field (DNA vaccines, recombinant proteins) are envisaged. The project, which falls within the scientific area of Medical Biotechnology, is headed by Gabriel Monteiro from BERG-iBB and Leonilde Moreira from BSRG-iBB.