SBIR-STTR Award

A novel bioprocess platform, involving synthesis of peptide and protein biopharmaceutical products as fusions with a synthetic "anchor" protein in bacteria, and subsequent proteolytic cleavage, will be developed. The unique features of the system allow for the economical production of large quantities of simple linear peptides, as well as complex, multi-component peptides. Proof of concept will be demonstrated by synthesizing three peptides of varying sizes; a 12-mer anti-fungal peptide, a 40-mer psalmotoxin, and an 86-mer, pro-insulin. Preliminary studies and cost projections suggest that peptides ranging from about 8 to 100 amino acids can be produced for a few dollars per gram, in contrast to chemical synthetic methods for which costs dramatically increase with the length of the peptide product. Another major advantage is the rapidity with which each product can be generated and the generic nature of the process for many peptide and protein products, facilitating scale-up. Additionally, the three peptide products have their own inherent commercial value. A more efficient bioprocess for human insulin can help meet growing demand. Diabetes is a growing worldwide epidemic that is particularly severe in the U.S and a more efficient bioprocess for human insulin would be immediately useful. This novel, rapid, economical, GMP- enabled bioprocess platform for recombinant peptides and proteins can help meet production requirements, at all levels of production from research quantities to kilograms, in the biopharmaceutical, vaccine, biodefense, and biomedical research industries. The economy and speed with which novel peptides and proteins may be produced from a UBL-type expression system and solid matrix UBL protease fill a great need in industry and could also address some of the government's biodefense requirements for very rapid production of large quantities of vaccines and biopharmaceuticals. Kits for production of peptide libraries based on the UBL expression system could also be of significant value to the biomedical research community. To develop this system and demonstrate its potential, we will synthesize three peptides, each of commercial interest, including human insulin for treatment of diabetes, psalmatoxin peptide for pain research, and MUC7 peptide for treatment of fungal infections.

A novel bioprocess platform, involving synthesis of peptide and protein biopharmaceutical products as fusions with a synthetic ""anchor"" protein in bacteria, and subsequent proteolytic cleavage, has been developed. The unique features of the system allow for the economical production of large quantities of simple linear peptides, as well as complex, multi-component peptides. Preliminary studies and cost projections suggest that peptides ranging from about 15 to 100 amino acids can be produced for a few dollars per gram, in contrast to chemical synthetic methods for which costs dramatically increase with the length of the peptide product. Another major advantage is the rapidity with which each product can be generated and the generic nature of the process for many peptide and protein products, facilitating scale-up. This novel, rapid, economical bioprocess platform for recombinant peptides and proteins can help meet production requirements, at all levels of production from research quantities to many kilograms, in the biopharmaceutical, vaccine, biodefense, and biomedical research industries.

Public Health Relevance:
A novel production platform is being developed and specifically tailored for the rapid, scaleable, and economical synthesis of large peptides and small proteins for which chemical synthesis and existing recombinant methods are not feasible. The technology addresses a significant unmet need for production of peptide product candidates in the 20-100 amino acid size range. There are numerous commercial applications for this technology in manufacturing of peptide therapeutics and vaccines, in conformational epitope discovery and production (for biodefense), and in biomedical research. The platform may even be cost efficient enough to help retain bio-manufacturing capacity in the US, despite the pressures of cheaper labor and operating costs elsewhere in the global economy. The platform also represents an environmentally friendly alternative to chemical peptide synthesis, which generates large volumes of organic waste.

Thesaurus Terms:
Address; Affinity; Amino Acids; Antigenic Determinants; Assay; Bacteria; Binding; Binding (Molecular Function); Binding Determinants; Bioassay; Biologic Assays; Biologic Products; Biological Agent; Biological Assay; Biological Products; Biomedical Research; Cells; Chemicals; Chimera Protein; Chimeric Proteins; Chitin; Chromatography; Chromatography / Separation Science; Chromatography, High Performance Liquid; Chromatography, High Pressure Liquid; Chromatography, High Speed Liquid; Complex; Culture Media; Development; Dextrans; Drugs, Nonproprietary; E Coli; Endotoxins; Epitopes; Escherichia Coli; Esteroproteases; Fermentation; Fusion Protein; Generalized Growth; Generic Drugs; Growth; Hplc; High Pressure Liquid Chromatography; Histidine; Histidine, L-Isomer; Humulin R; In Vitro; Industry; Insulin; Insulin (Ox), 8a-L-Threonine-10a-L-Isoleucine-30b-L-Threonine-; Insulin, Regular; Ions; Kilogram; Knock-Out; Knockout; L-Histidine; Laboratories; Length; Metals; Methods; Molecular Interaction; Monitor; N-Terminal; Nh2-Terminal; Nature; Novolin R; Nucleic Acids; Peptidases; Peptide Hydrolases; Peptide Synthesis; Peptides; Phase; Plant Resins; Preparation; Pressure; Pressure- Physical Agent; Process; Production; Proteases; Proteinases; Proteins; Proteolytic Enzymes; Quality Control; Reaction; Reagent; Recombinants; Recovery; Research; Resins, Plant; Solubility; Strepavidin; Streptavidin; System; System, Loinc Axis 4; Technology; Temperature; Testing; Tissue Growth; Vaccines; Work; Aminoacid; Aqueous; Biodefense; Biopharmaceutical; Bioprocess; Biotherapeutic Agent; Chemical Synthesis; Commercial Application; Commercialization; Cost; Cost Efficient; Dextran; Gene Product; Generic; Growth Media; In Vivo; Maltose-Binding Protein; Meetings; New Approaches; Novel; Novel Approaches; Novel Strategies; Novel Strategy; Ontogeny; Peptide Chemical Synthesis; Pressure; Prevent; Preventing; Protein Chemical Synthesis; Public Health Relevance; Recombinant Peptide; Resin; Scale Up; Therapeutic Vaccine; Tool; Wasting