Strain Development Service
BOC Sciences offers strain development and strain improvement services to enhance their metabolic capacities. With over 20 years of experience in traditional strain technology, we are capable of providing our customers with ideal strains whose advantages include rapid growth, genetic stability, and reduction of cultivation costs. Our strain development and improvement services cover various microbial systems, including Escherichia coli, streptomyces, actinomyces, mycobacterium and Paracoccus, and the eukaryotic systems such as yeast (Pichia pastoris, saccharomyces cerevisiae), aspergillus, penicillium, acremonium, filamentous fungi and excavate.
Through advanced genetic engineering techniques combined with high-throughput screening and metabolic engineering our expert team develops customized strains to fulfill your specific needs. Our team maintains a collaborative relationship with you during every stage of development which includes initial consultation through strain delivery to ongoing support while assuring our services adhere to top quality standards and regulatory requirements. Our Strain Development Services offer solutions to improve fermentation efficiency and productivity for clients in pharmaceutical, biotechnology and food industries.
Our Technology
CRISPR/Cas9-Based Strain Engineering
Through CRISPR/Cas9 technology researchers can edit genomes precisely by using guide RNA (gRNA) to navigate the Cas9 enzyme toward exact genomic sites. CRISPR/Cas9-based strain engineering services enable customers to tailor microorganisms or cell lines through gene knockouts of harmful genes and the insertion of beneficial genes or correction of genetic mutations. Biopharmaceutical companies, synthetic biology researchers, and agricultural scientists use this service to create strains with particular characteristics including better metabolic product yields and superior stress resistance.
Directed Evolution Service
Directed evolution service reproduces natural selection in the lab through induced gene mutations and recombination followed by screening which speeds up the development of desired proteins or biological systems. Researchers often use this service to improve enzymes' catalytic efficiency, substrate specificity, and stability or to enhance microbial metabolic pathways. Directed evolution produces functional mutants by executing repeated mutation cycles and screenings and finds broad application in biocatalysis along with drug development and industrial fermentation processes.
Gene Editing Service
Gene editing services use advanced genetic engineering technologies, such as CRISPR/Cas9, TALEN, or ZFN, to make precise modifications to the genome of an organism. This service helps customers achieve gene knockout, knock-in, replacement, or repair, and is suitable for various fields including basic research, disease model creation, gene therapy, and bioengineering. Gene editing enables in-depth studies of gene function, development of new therapeutic strategies, or optimization of biological production efficiency.
Gene Mutation Service
Gene mutation services induce mutations in target genes or genomes using chemical mutagens, physical mutagenesis, or gene editing tools. This service is used to study gene function, explore the relationship between protein structure and function, or develop biologically relevant materials with new traits. For example, in drug development, inducing mutations can help screen strains resistant to drugs, thereby optimizing drug targets; in agriculture, it can be used to cultivate crops with superior traits.
Gene Overexpression Service
Gene overexpression services involve constructing expression vectors to introduce target genes into host cells or organisms, causing them to express at high levels under specific conditions. This service is widely used in protein production, metabolic engineering, and gene function research. For instance, in industrial fermentation, overexpressing key enzyme genes can increase the yield of target metabolic products; in basic research, overexpression can be used to study gene physiological functions or signaling pathways.
Genetic Recombination Service
Genetic recombination services involve integrating gene fragments from different sources into the target genome through in vitro recombination or in vivo homologous recombination. This service can be used to construct chimeric genes, optimize metabolic pathways, or develop biological systems with new functions. For example, in synthetic biology, genetic recombination can be used to assemble multiple biological components to create complex biosynthetic pathways for producing high-value chemicals or drugs.
High-Throughput Screening Service
High-throughput screening services are a fast and efficient technological platform used to screen large numbers of samples for target molecules, cells, or strains with specific functions or characteristics. This service typically combines automated equipment with advanced detection techniques, such as fluorescence analysis, mass spectrometry, or biosensors, enabling rapid processing and analysis of large datasets. It is widely applied in drug discovery, gene function research, and bioengineering optimization, such as screening novel enzyme inhibitors or optimizing microbial fermentation conditions.
Metabolic Engineering
Metabolic engineering is a systematic biotechnology approach that modifies the metabolic pathways of organisms to optimize their metabolic networks, improving the synthesis efficiency of target products or endowing organisms with new metabolic functions. Metabolic engineering services typically involve gene knockout, overexpression, introduction of foreign genes, and regulation of metabolic flux. For example, in industrial microorganisms, metabolic engineering can increase the yield of biofuels, amino acids, or antibiotics, or develop biological systems capable of utilizing non-traditional carbon sources.
Strain Systems For Fermentation
Fermentation strain system services focus on developing and optimizing microorganisms used in industrial fermentation. Through genetic modification, adaptive evolution, or strain screening, these services can provide strains with high yield, stability, and good fermentation performance. For example, in the food, pharmaceutical, and biofuel industries, optimized fermentation strains can improve production efficiency, reduce costs, and minimize environmental pollution. Additionally, fermentation strain system services can also provide solutions for fermentation process optimization and scale-up production.
Transfection Service
Transfection services are a technique for introducing foreign nucleic acids (such as DNA, RNA, or plasmids) into cells, widely applied in gene function research, protein expression, and cell therapy. Transfection can be achieved through chemical methods (such as lipid-mediated transfection), physical methods (such as electroporation), or viral vector-mediated methods for efficient nucleic acid delivery. For example, in basic research, transfection can be used to study gene expression regulation mechanisms; in clinical applications, transfection technology can be used to develop gene therapy drugs or cell therapy products.
The Role of Strains in Fermentation
Strains are the core of the fermentation process, directly determining the efficiency and quality of product formation. In the fermentation process, the strain's metabolic capacity, growth rate, and genetic stability are crucial factors affecting production efficiency and product quality. Through strain development, we can optimize these characteristics to meet specific production needs, such as increasing the yield of target products, improving substrate utilization, and enhancing tolerance to process conditions.
Importance of Strains Development
Enhanced Productivity: They enable the optimization of microbial strains to increase the yield of target products, such as pharmaceuticals, biofuels, enzymes, and chemicals. This can significantly improve the efficiency of industrial production processes.
Improved Product Quality: By developing strains with specific characteristics, it is possible to enhance the quality and consistency of the final product. This can lead to better performance and customer satisfaction.
Cost Reduction: Strain development can help reduce production costs by improving the efficiency of the fermentation process, reducing the need for expensive raw materials, and minimizing waste.
Metabolic Engineering: These services allow for the manipulation of metabolic pathways to redirect the flow of metabolites towards the production of desired compounds. This can lead to the development of novel products or the improvement of existing ones.
Adaptation to Environmental Conditions: Strain development can help create strains that are more resilient to harsh environmental conditions, such as high temperatures, extreme pH levels, or the presence of inhibitors. This can improve the robustness of the production process.
Customization: Strain Development Services can be tailored to meet the specific needs of each client, ensuring that the developed strains are perfectly suited for their particular application.
Methods for strain development
Strain development in fermentation is a complicated process that combines traditional microbiological approaches with current genetic engineering and bioprocess optimization. The procedure involves various processes and approaches for improving the genetic and phenotypic characteristics of microbial strains.
Traditional methods are used for strain development
Traditionally, strain development is performed by random mutation and screening or selection, known as the classical technique. This empirical approach has been used for over 50 years and has a proven track record of effectiveness. The best-known example is the titer improvement for penicillin. Given its lengthy history, the classical technique remains the principal strain improvement strategy for each newly founded strain development program. The classical technique remains popular since it does not require prior understanding of the metabolite metabolic process, regulation, or transport. Another explanation is that advances in the accuracy and sensitivity of analytical equipment throughout time have significantly increased detection reliability and sensitivity. Furthermore, automation and downsizing of screening methods have greatly decreased system variability while increasing screening throughput.
(1) The first stage entails the thorough selection of a parent strain, which can be either a wild-type strain, chosen for its naturally occurring desirable qualities, or a laboratory strain, recommended for its genetic stability and detailed characterization within scientific literature.
(2) Genetic manipulation techniques: To produce a vast range of genetic variety, mutations can be introduced deliberately or spontaneously. To produce this genetic variety, chemical mutagenesis, UV radiation, and transposon mutagenesis are frequently used techniques. Under selection pressures, microorganisms are cultivated to generate advantageous features, such improved resilience under process conditions or greater product production.
(3) Random screening: After being separated, mutation survivors are grown on either liquid or solid agar substrate to create separate colonies. In small-scale fermentation tanks, single colonies are selected at random and fermented. It is more probable to uncover mutants with a slight productivity gain rather than a high-producing, blockbuster mutation while looking for mutants with higher productivity. To detect mutants with a tiny titer increase, nevertheless, the screening method has to be sensitive and consistent enough to lessen the possibility of discovering fake mutants.
The process for selecting improved strains. (Parekh S., et al., 2000)
Genetic engineering for strain development
Genetic engineering is currently a common method of deriving better microbial strains. This strategy has a variety of benefits, such as the ability to specifically regulate both desired and helpful genes, the reduction of the number of mutants tested, and the creation of several beneficial mutations. It is necessary to have prior understanding of the metabolic process in order to apply this strategy, though. Furthermore, the availability of genetic tools is necessary for the manipulation of the generating organism.
Transformation is the most common technique for introducing DNA into bacteria. In order for transformation to occur, recipients must absorb plasmid DNA during a physiological period of competence, which typically happens at a certain growth stage. On the other hand, naturally occurring competence-based DNA absorption is typically ineffective. Chemical treatments of bacterial cells that promote DNA absorption can produce competence. Plasmid DNA absorption in Escherichia is facilitated by pretreating cells with either calcium chloride or rubidium chloride. Plasmid DNA transformation into the species Streptomyces, which makes most antibiotics, is more intricate than that of Escherichia. Protoplasts are prepared by lysozyme-treating mycelia to remove the majority of the cell wall. To facilitate DNA absorption, plasmid DNA is combined with protoplasts in the presence of polyethylene glycol (PEG). When double-stranded plasmid DNA is employed, substantial restriction barriers in some Streptomyces species prevent effective protoplast transformation. Sometimes using single-stranded plasmid DNA can solve this issue.
Conjugation is an additional technique for plasmid DNA introduction into microorganisms. This technique uses a donor strain that has the desired gene(s), the origin of transfer (oriT) on a plasmid, and the chromosomal genes encoding transfer functions. DNA is transferred when the donor and receiver come into short touch. Following conjugation, recipient cells become resistant to the antibiotic used to destroy the donor cells. The plasmid's antibiotic resistance marker is used to identify recipient cells that will receive the transplanted plasmid.
An alternate technique to PEG-mediated DNA uptake is electroporation. When recipient cells are exposed to ultrasonic pulses in the presence of plasmid DNA, the cells become electrocompetent. The electroshock causes transient holes in the cell membrane, which open up for DNA absorption. By introducing new genes or altering existing ones, advanced molecular tools like plasmids, CRISPR-Cas9, and other gene-editing technologies are used to improve the strain's capabilities.
Industrial production model. (Liu J., et al., 2022)
Our Services
Strain Selection and Optimization: Based on the target product and production requirements, we select suitable parent strains and perform genetic manipulation to introduce desirable traits.
Genetic Engineering: Using advanced techniques such as gene editing (e.g., CRISPR-Cas9), we modify the strain's genetic material to enhance its metabolic pathways and production capabilities.
High-Throughput Screening: We employ high-throughput screening methods, such as agar plate-based screening, fluorescence-activated cell sorting, and droplet microfluidic screening, to identify and select high-performance strains.
Fermentation Process Optimization: After obtaining the optimized strain, we further optimize the fermentation process, including medium composition, fermentation conditions, and scale-up strategies, to maximize product yield and quality.
Strain Preservation and Stability Testing: Establish and maintain strain banks, conduct stability studies, and ensure the safe and reliable delivery of strains.
Our Advantages
Over 20 Years of Experience: We have extensive experience in traditional strain breeding and genetic engineering, enabling us to provide high-quality strain development services.
Advanced Genetic Engineering Techniques: We utilize cutting-edge genetic engineering tools, such as CRISPR-Cas9, to achieve precise and efficient strain modification.
High-Throughput Screening Capabilities: Our high-throughput screening platforms allow for rapid identification and selection of high-performance strains, significantly reducing development time.
Comprehensive Fermentation Process Optimization: We have a deep understanding of fermentation process optimization, ensuring that the developed strains can be effectively scaled up and applied in industrial production.
Quality Assurance: All our strains are tested and released in strict accordance with regulatory requirements, ensuring their purity, stability, and reliability.
Our Service Process
1. Initial Consultation and Project Assessment
2. Strain Selection and Optimization
3. Fermentation Process Optimization
4. Strain Preservation and Stability Testing
5. Quality Control and Documentation
6. Delivery and Support
FAQ
1. What types of microorganisms can be used for strain development?
Strain development can be applied to a wide range of microorganisms, including bacteria (such as E. coli, Bacillus subtilis, Streptomyces), yeast (such as Saccharomyces cerevisiae, Schizosaccharomyces pombe), and other fungi. The choice of microorganism depends on the specific application and the desired product.
2. What are the common methods used in strain development?
Common methods include genetic engineering (such as gene knockout, overexpression, and CRISPR-Cas9 editing), random mutagenesis (using physical or chemical mutagens), directed evolution, metabolic engineering, adaptive laboratory evolution, protoplast fusion, and site-directed mutagenesis. These methods can be used individually or in combination to achieve the desired strain characteristics.
3. How long does the strain development process take?
The duration of the strain development process depends on the complexity of the project, the specific techniques used, and the desired outcomes. It can range from several weeks to several months. Factors such as the availability of the parent strain, the efficiency of the genetic modifications, and the screening process can all affect the timeline.
4. What are the safety considerations for modified strains?
Strain development service providers follow strict safety protocols and regulatory requirements to ensure that the modified strains are safe for use in various applications. This includes assessing the potential risks associated with the genetic modifications and ensuring that the strains do not pose any environmental or health hazards.
5. Can strain development improve the yield of the target product?
Yes, one of the main goals of strain development is to enhance the production yield of the target product. This can be achieved through various methods, such as optimizing metabolic pathways, increasing the expression of key genes, and improving the overall fitness of the microorganism.
6. What is the role of high-throughput screening in strain development?
High-throughput screening plays a crucial role in strain development by allowing the rapid identification and selection of strains with desired characteristics. This method involves testing large libraries of genetic variants under controlled conditions to identify the most promising candidates for further development.
7. How is the stability of the developed strain ensured?
The stability of the developed strain is ensured through rigorous testing and characterization. This includes evaluating the genetic stability of the strain under different storage and fermentation conditions, as well as conducting long-term stability studies. Strain preservation methods, such as cryopreservation, are also used to maintain the viability and stability of the strain over time.
8. Can strain development be customized for specific applications?
Yes, strain development services can be customized to meet the specific needs of each client. This includes tailoring the genetic modifications, fermentation conditions, and downstream processing steps to optimize the production of the target product for a particular application.
