Implementation of the agmatine-controlled expression system for inducible gene expression in Lactococcus lactis

[Background] Lactococcus lactis has been safely consumed in fermented foods for millennia. This Gram-positive bacterium has now become of industrial importance as an expression host for the overproduction of lipopolysaccharide-free recombinant proteins used as food ingredients, therapeutic proteins and biotechnological enzymes.[Results] This paper reports an agmatine-controlled expression (ACE) system for L. lactis, comprising the lactococcal agmatine-sensor/transcriptional activator AguR and its target promoter P aguB . The usefulness and efficiency of this system was checked via the reporter gene gfp and by producing PEP (Myxococcus xanthus prolyl-endopeptidase), an enzyme of biomedical interest able to degrade the immunotoxic peptides produced during the gastrointestinal breakdown of gluten.[Conclusion] The ACE system developed in this work was suitable for the efficient expression of the functional recombinant proteins GFP and PEP. The expression system was tightly regulated by the agmatine concentration and allowed high protein production without leakiness.This work was performed with the financial support of the Spanish Ministry of Economy and Competitiveness (AGL2013-45431-R), the Principality of Asturias Plan for Science, Technology and Innovation 2013-2017, and FEDER funds (GRUPIN14-137). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). P.A.S. was the beneficiary of a fellowship from the FICYT, Principality of Asturias, Spain (BP09093). D.M.L. and B.d.R. were beneficiaries of JAE DOC contracts (CSIC).Peer Reviewe