ArticleApplied and environmental microbiology2014
Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris.
Article in Applied and environmental microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Turbid but accurate: automating lysostaphin quantification including uncertainty quantification.Microbial cell factories · 2026Article
- Development of Efficient Expression Systems for Bacteriolytic Proteases L1 and L5 ofInternational journal of molecular sciences · 2025Article
- EngineeringEngineering microbiology · 2024Review
- The First Homologous Expression System for the β-Lytic Protease ofInternational journal of molecular sciences · 2022Article
- Heterologous production of active form of beta-lytic protease by Bacillus subtilis and improvement of staphylolytic activity by protein engineering.Microbial cell factories · 2021Article
- Production of Industrial Enzymes via Pichia pastoris as a Cell Factory in Bioreactor: Current Status and Future Aspects.The protein journal · 2021Review
- Electrostatic-Mediated Affinity Tuning of Lysostaphin Accelerates Bacterial Lysis Kinetics and EnhancesAntimicrobial agents and chemotherapy · 2021Article
- Deimmunized Lysostaphin Synergizes with Small-Molecule Chemotherapies and Resensitizes Methicillin-ResistantAntimicrobial agents and chemotherapy · 2021Article
- Design and High Expression of Non-glycosylated Lysostaphins inFrontiers in microbiology · 2021Article
- Globally deimmunized lysostaphin evades human immune surveillance and enables highly efficacious repeat dosing.Science advances · 2020Article
- Selective Eradication ofAntibiotics (Basel, Switzerland) · 2020Article
- Production of Lysostaphin by Nonproprietary Method Utilizing a Promoter from Toxin-Antitoxin System.Molecular biotechnology · 2019Article
- High-fidelity PCR enzyme with DNA-binding domain facilitates de novo gene synthesis.3 Biotech · 2017Article
- EpiSweep: Computationally Driven Reengineering of Therapeutic Proteins to Reduce Immunogenicity While Maintaining Function.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Enhanced secretion of a methyl parathion hydrolase in Pichia pastoris using a combinational strategy.Microbial cell factories · 2015Article
- Depletion of T cell epitopes in lysostaphin mitigates anti-drug antibody response and enhances antibacterial efficacy in vivo.Chemistry & biology · 2015Article
- Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently.Chemical Society reviews · 2015Review
- Structure-based redesign of lysostaphin yields potent antistaphylococcal enzymes that evade immune cell surveillance.Molecular therapy. Methods & clinical development · 2015Article
- Fusion with a cell wall binding domain renders autolysin LytM a potent anti-Staphylococcus aureus agent.FEMS microbiology letters · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.