ArticleApplied and environmental microbiology2001
Signal peptide and propeptide optimization for heterologous protein secretion in Lactococcus lactis.
Article in Applied and environmental microbiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 130 citations in OpenAlex.
- Exploration of endogenous signal peptides and tandem linkage strategies for enhanced heterologous protein secretion inSynthetic and systems biotechnology · 2026Article
- PEARL: Protein Eluting Alginate with Recombinant Lactobacilli.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Review
- An inverse relationship between fitness and secretion efficiency in a gram-positive bacterium.PNAS nexus · 2025Article
- Roles of Mature Domain Targeting Signals (MTSs) for Protein Translocation and Secretion inInternational journal of molecular sciences · 2024Article
- Co-expression of endoglucanase and cellobiohydrolase from yak rumen in lactic acid bacteria and its preliminary application in whole-plant corn silage fermentation.Frontiers in microbiology · 2024Article
- Expression of β-Glucosidases from the Yak Rumen in Lactic Acid Bacteria: A Genetic Engineering Approach.Microorganisms · 2023Article
- Effect of Secretion Efficiency of Mutant KRAS Neoantigen byInternational journal of molecular sciences · 2023Article
- Oral glucagon-like peptide 1 analogue ameliorates glucose intolerance in db/db mice.Biotechnology letters · 2022Article
- Optimization of Signal Peptide via Site-Directed Mutagenesis for Enhanced Secretion of Heterologous Proteins inInternational journal of molecular sciences · 2022Article
- Synthetic pro-peptide design to enhance the secretion of heterologous proteins by Saccharomyces cerevisiae.MicrobiologyOpen · 2022Article
- Genome-wide high-throughput signal peptide screening via plasmid pUC256E improves protease secretion in Lactiplantibacillus plantarum and Pediococcus acidilactici.BMC genomics · 2022Article
- Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses ofFrontiers in bioengineering and biotechnology · 2020Review
- Engineering integrative vectors based on phage site-specific recombination mechanism for Lactococcus lactis.BMC biotechnology · 2019Article
- Construction of a shuttle expression vector for lactic acid bacteria.Journal, genetic engineering & biotechnology · 2019Article
- Genetics of Lactococci.Microbiology spectrum · 2019Review
- Production of Phytase Enzyme by a Bioengineered Probiotic for Degrading of Phytate Phosphorus in the Digestive Tract of Poultry.Probiotics and antimicrobial proteins · 2019Article
- Screening for New Surface Anchoring Domains forFrontiers in microbiology · 2019Article
- Enhancement of lignocellulosic degradation in high-moisture alfalfa via anaerobic bioprocess of engineeredBiotechnology for biofuels · 2019Article
- Engineering recombinant Lactococcus lactis as a delivery vehicle for BPC-157 peptide with antioxidant activities.Applied microbiology and biotechnology · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactic acid bacteria are food-grade microorganisms that are potentially good candidates for production of heterologous proteins of therapeutical or technological interest. We developed a model for heterologous protein secretion in Lactococcus lactis using the staphylococcal nuclease (Nuc). The effects on protein secretion of alterations in either (i) signal peptide or (ii) propeptide sequences were examined. (i) Replacement of the native Nuc signal peptide (SP(Nuc)) by that of L. lactis protein Usp45 (SP(Usp)) resulted in greatly improved secretion efficiency (SE). Pulse-chase experiments showed that Nuc secretion kinetics was better when directed by SP(Usp) than when directed by SP(Nuc). This SP(Usp) effect on Nuc secretion is not due to a better antifolding activity, since SP(Usp):Nuc precursor proteins display enzymatic activity in vitro, while SP(Nuc):Nuc precursor proteins do not. (ii) Deletion of the native Nuc propeptide dramatically reduces Nuc SE, regardless of which SP is used. We previously reported that a synthetic propeptide, LEISSTCDA, could efficiently replace the native Nuc propeptide to promote heterologous protein secretion in L. lactis (Y. Le Loir, A. Gruss, S. D. Ehrlich, and P. Langella, J. Bacteriol. 180:1895-1903, 1998). To determine whether the LEISSTCDA effect is due to its acidic residues, specific substitutions were introduced, resulting in neutral or basic propeptides. Effects of these two new propeptides and of a different acidic synthetic propeptide were tested. Acidic and neutral propeptides were equally effective in enhancing Nuc SE and also increased Nuc yields. In contrast, the basic propeptide strongly reduced both SE and the quantity of secreted Nuc. We have shown that the combination of the native SP(Usp) and a neutral or acidic synthetic propeptide leads to a significant improvement in SE and in the quantity of synthesized Nuc. These observations will be valuable in the production of heterologous proteins in L. lactis.
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