CD BioGlyco provides a world-class genomics-based chassis strain screening service designed to identify and validate high-performance microbial platforms for the production of complex glycans, glycoproteins, and glycolipids. By leveraging advanced genomic sequencing and bioinformatics, we move beyond traditional trial-and-error methods. Our service focuses on the deep exploration of genetic backgrounds to match specific glycoengineering goals with the most compatible cellular environments. Whether you are developing human-like N-glycan structures in bacteria or optimizing yeast for high-yield human milk oligosaccharides (HMO) production, our genomics-driven approach ensures that your chassis possesses the necessary metabolic flux, genetic stability, and post-translational machinery to succeed.
Key Technologies
Next-Generation Sequencing (NGS) & De Novo Assembly
We employ high-throughput NGS to map the entire genome of candidate strains. This allows us to identify endogenous glycosyltransferases, glycosidases, and metabolic pathways that might interfere with or enhance the production of target glycoconjugates.
Comparative Genomics & Metabolic Modeling
By comparing the genomes of various candidates against our proprietary database, we predict the metabolic capacity and genetic robustness of a strain. We use computational models to simulate how heterologous glycan pathways will integrate into the host's existing network.
Gene Screening Integration
For advanced projects, we combine genomics with functional screening using gene editing libraries. This allows us to identify specific gene clusters that, when modified, improve the yield and fidelity of the target glycan product.
Precision Genomics: The Blueprint for Superior Glycan Cell Factories
At CD BioGlyco, our genomics-based chassis strain screening service is a solution designed to bridge the gap between theoretical pathway design and industrial-scale reality. We recognize that even the most elegantly designed synthetic pathway can fail if placed in a hostile or incompatible chassis. Our service scope is structured to mitigate these risks by providing a data-driven foundation for strain selection.
We support a vast array of chassis types, including traditional models like Escherichia coli and Saccharomyces cerevisiae, as well as non-traditional hosts such as Pichia pastoris, Bacillus subtilis, and various insect or mammalian cell lines. Our process begins with a detailed assessment of the client's target molecule, whether it is a specific HMO, a complex polysaccharide, or a therapeutic glycoprotein.
Our genomic analysis delves into the "Genetic Inventory" of potential strains, looking for specific markers:
Precursor Availability
Does the strain naturally produce high levels of UDP-Glc, GDP-Man, or CMP-Neu5Ac?
Product Stability
Are there endogenous proteases or glycosidases that might degrade the target molecule?
Genomic Plasticity
How easily can the strain accept large multigene cassettes for complex glycan biosynthesis?
Beyond simple identification, we provide detailed implementation strategies. This includes recommending specific promoters, integration sites, and "knock-out" targets revealed by our genomic screening. By utilizing our service, clients receive more than just a list of strains; they receive a validated biological platform optimized for their specific biosynthetic requirements, significantly reducing R&D timelines and increasing the probability of commercial success.
Workflow
Project Consultation and Target Definition
We begin by defining the target glycan or glycoprotein's structural requirements. Our experts work with you to establish key performance indicators (KPIs) such as minimum yield, specific linkage requirements, and tolerance parameters for the final production process.
Genomic Library Construction and Sequencing
CD BioGlyco collects or constructs a diverse library of candidate chassis strains. We then perform whole-genome sequencing (WGS) using NGS platforms to establish a high-resolution genetic map for every candidate in the library.
Bioinformatic Comparative Analysis
Using advanced bioinformatics pipelines, we screen the sequenced genomes for metabolic compatibility. We identify "bottleneck" genes and endogenous pathways that could compete for precursors, ensuring the selected chassis has a "clean" background for glycoengineering.
Metabolic Flux Prediction
We utilize in silico metabolic modeling to simulate the integration of your target pathway into the top-ranking genomic candidates. This step predicts the metabolic burden and identifies necessary genomic modifications to optimize energy and carbon flow toward glycan synthesis.
Phenotypic Validation and Small-Scale Testing
The top genomic candidates undergo empirical testing. We perform small-scale cultivations to correlate the genomic findings with actual growth kinetics, genetic stability, and initial expression levels of the target molecule.
Comprehensive Screening Report and Recommendation
The final stage involves the delivery of a detailed report. This includes the genomic profiles, comparative data, and a formal recommendation of the "Best-Fit" chassis, along with a roadmap for further strain optimization and scale-up.
Publication Data
DoI: 10.3390/microorganisms10010047
Journal: Microorganisms
IF: 4.2
Published: 2022
Results: This study presents genomic characterization and streamlined genome chassis construction of Lactococcus lactis N8, a nisin Z-producing strain. WGS reveals N8 has a 2.42 Mb genome (35.1% GC content) with 2434 coding sequences, two large megaplasmids (pLLN8-1, pLLN8-2) involved in sugar metabolism and stress resistance, seven prophage-related fragments (8.98% of the genome), and 12 genomic islands. It also harbors a hybrid NRPS-PKS system for secondary metabolite synthesis and two bacteriocin gene clusters. Using Cre-loxP-mediated deletion of nonessential regions (prophages, genomic islands), the authors constructed a streamlined chassis (N8-8) with 176.43 kb deleted (6.86% of the genome), the largest deletion reported for L. lactis to date. The chassis shows shortened generation time (17.18% reduction) and unaltered nisin production, laying a foundation for L. lactis applications in synthetic biology and metabolic engineering.
Fig.1 Circular genome plot of L. lactis N8. (Qiao, et al., 2022)
Applications
Biopharmaceutical Manufacturing
Identification of optimized yeast and mammalian chassis for the production of monoclonal antibodies (mAbs) and recombinant proteins with humanized, non-immunogenic glycosylation patterns to ensure therapeutic safety and efficacy.
Nutraceutical & HMO Production
Screening microbial strains like E. coli or B. subtilis for high-yield production of HMOs, ensuring cost-effective and scalable synthesis for infant formula and health supplements.
Vaccine Development
Selection of robust chassis for the expression of glycoconjugate vaccines, focusing on strains that provide high surface display of antigens or efficient secretion of glycosylated viral subunits.
Industrial Enzyme Engineering
Development of fungal and bacterial cell factories for the large-scale production of glyco-active enzymes used in the textile and biofuel industries, prioritizing strains with high protein secretion capacity.
Advantages
Deep Glycobiology Expertise
Our team possesses specialized knowledge in glycan biosynthesis, allowing us to interpret genomic data through the specific lens of carbohydrate chemistry and enzyme kinetics.
High-Throughput Capabilities
Our facility is equipped with automated NGS and liquid handling systems, enabling the simultaneous screening of hundreds of candidate strains without compromising data quality or precision.
Customized Screening Modules
We do not offer a "one-size-fits-all" solution. Each screening project is tailored to the specific metabolic requirements of the client's final application.
Seamless Integration
As a full-service provider, the results from our genomic screening are directly integrated into our downstream strain development, fermentation optimization, and purification services.
Frequently Asked Questions
Customer Review
"The genomic screening provided by CD BioGlyco was a turning point for our HMO project. We had been struggling with low yields in E. coli for months. Their analysis identified a previously unknown endogenous glycosidase in our strain that was degrading the product. Switching to their recommended chassis tripled our output immediately."
– G.H., Director of R&D
"We needed a robust yeast chassis for a complex glycoprotein vaccine. CD BioGlyco's comparative genomics platform identified a Pichia variant with superior protein folding markers that we hadn't considered. The data-driven approach gave us the confidence to move into pilot scale much faster."
– Q.C., Senior Scientist
"Professional, thorough, and highly insightful. The team at CD BioGlyco doesn't just deliver data; they deliver actionable biological solutions. Their expertise in synthetic glycobiology is truly unparalleled in the industry."
CD BioGlyco's genomics-based chassis strain screening service represents the cutting edge of synthetic biology. By combining deep genomic insights with practical glycoengineering expertise, we provide our clients with the robust, high-performance cellular platforms needed to lead the next generation of biomanufacturing. Please feel free to contact us to help you design the optimal screening strategy for your unique goals.
Reference
Qiao, W.; et al. Genomic features and construction of streamlined genome chassis of nisin Z producer Lactococcus lactis N8. Microorganisms. 2022, 10: 47. (Open Access)
For research use only. Not intended for any clinical use.
Fig.1 Circular genome plot of L. lactis N8. (Qiao, et al., 2022)
