Microbial strain improvement and bioprocess development services

Annotation

Slovenian SME has developed a highly efficient high-throughput strain improvement and process development program to rapidly increase the yield target biosynthetic products or improve the impurity profile of produced target compounds. The company offers optimized bioprocess which are developed up to the pilot scale in accordance with customer's specifications and the possibility for industrial sized scale-up. Services agreement or subcontracting is sought by the company.

Offer description

Slovenian SME has developed an efficient high-throughput strain improvement and process development program, which can significantly increase the yield of the client’s target product or improve the impurity profile of the target compounds. The optimized bioprocess is developed up to the pilot scale in accordance with customer's specifications with the possibility for scale-up support to industrial production scale. The following approaches to strain improvement are utilized: • smart random mutagenesis and high-throughput strain selection using a combination of classical and so called “rational mutagenesis” and metabolic pressure as well as genome shuffling/protoplast fusion approaches, • biosynthetic/metabolic engineering of identified target pathways, using over-expression of target genes and entire biosynthetic clusters and/or inactivation of competing or undesired metabolic pathways, • heterologous expression of entire target biosynthetic pathways in a high-producing heterologous host strain, such as industrial actinomyces, Bacillus, E.coli, yeast etc. Genomics, transcriptomics and proteomics approaches in identification of key metabolic pathways involved in the biosynthesis of target products or undesired impurities are utilized. In parallel with strain improvement, company develops and optimizes the fermentation process including cultivation conditions, media, process parameters, ...etc. up to 150 litres pilot scale. Company's engineers have extensive experience in technology transfer and successful scaling up of developed fermentation technologies which are done at client’s production facilities. Industrial strain improvement and process development programs are done by the company, not excluding even some of the most exotic microbial strains. A fully integrated after sales program is available. The company has decades of experience in the field of industrial strain improvement programs and routine manipulation of a number of different bacterial species (E.coli, Bacillus, actinomycetes, myxobacteria, yeasts, etc.). Using specially optimized mutagenesis, strain selection protocols, in-house developed molecular biology tools and techniques, allow the company to efficiently engineer and improve target strains at a very high success rate and rapid development time frames. A highly efficient expression vectors for heterologous expression of gene clusters encoding complex biosynthesis of secondary metabolites were developed, as well as heterologous protein/enzyme expression. Type of partnership sought by the company is services agreement. Subcontracting is also a type of partnership suitable to the company.

Innovations and advantages

The company offers three types of approaches to microbial strain improvement and bioprocess development. The main advantages of each approach are listed below: A) Classical Approach – strain selection advantages • classical mutagenesis and high-throughput strain selection and analytics • directed mutagenesis by metabolic pressure • scale-down process optimization • starting from existing technologies or from wild type strains B) Genetic Approach – metabolic engineering advantages • increasing precursor supply • up / down-regulation of genes and/or pathways • removing competing metabolic pathways and impurities C) Heterologous expression – alternative approach for selected metabolites • in-house developed cloning platform for mobilization and heterologous expression of entire biosynthetic pathways • expression of target metabolites in a known industrial microbial host with defined process parameters possibility to introduce additional modifications into the cloned biosynthetic pathway Although each strain improvement / strain development project is unique, typically the key elements of company's strain improvement program would include the following advantages: • whole-genome sequencing and bio-informatics analysis of the starting strain • scaling-down the bio-process to obtain reproducible high-throughput screening at smallest possible scale • classical and directed mutagenesis combined with high-throughput screening • genetic/metabolic engineering (if genetically modified organisms (GMO) are acceptable for the client) • optimization and stability testing of improved candidate strains • potential media and process re-optimization • scale-up to high-volume fermentation The before mentioned steps lead to reduction in time necessary for the strain improvement/development. Strain improvement projects are generally supported by whole genome analysis and bioinformatics support.

Technology keywords

06002002 Cellular and Molecular Biology
06002004 Protein Engineering
06002005 Genetic Engineering
06002008 Microbiology
06003002 Gene Expression, Proteom Research

Market application codes

04001002 Industrial genetic engineering applications
04007 Enzymology/Protein Engineering/Fermentation
04008 Genetic Engineering
04010 Microbiology
04015 Gene Expression, Proteome Research

Intellectual property rights

Secret Know-how

Profile date

16.03.2019