Biomanufacturing for applied markets

Synthetic biology is growing in importance globally, as companies strive to reduce their carbon footprints and achieve net zero goals. Bioengineering has long been used in the pharma industry, and this expertise is transferable to applied markets, such as the biofuels, agrochemicals, food and beverage, cosmetics, materials, vitamins and probiotics sectors. Manufacturers are increasingly moving away from purchasing commercially available strains, turning instead to in-house strain development and using genomic techniques such next-generation sequencing (NGS) in upstream process development. Maria Savino, Global Segment Development Manager for Biomanufacturing at Beckman Coulter Life Sciences, discusses the various stages of biomanufacturing, and how Beckman Coulter can help.

Almost every industrial sector is under pressure to adapt manufacturing workflows to reduce their carbon footprints and meet the 2030 and 2050 targets set out as part of the Net Zero Roadmap. The challenge for manufacturers is to develop the same product using bioreplacement materials and/or by establishing net zero production processes. The perfume industry is a good example of this; instead of producing a scent from acres of cultivated flowers, the gene that creates that specific aroma can now be inserted into a bacteria or yeast strain for an efficient biomanufacturing workflow. This strain can then be scaled up to produce a large quantity of the compound of interest.

NGS technologies have long played a crucial role in the biopharma industry, offering a key validation tool suitable for any type of engineered cell. This powerful technique is equally important in biomanufacturing applications¹ for applied markets, where synthetic biology processes are used to generate organisms containing novel genetic sequences or intentional mutations. NGS analysis provides assurance that the engineered cell lines will behave as intended for the entire lifecycle of a product or process. Parallelization is another advantage, as sufficient individual sequencing reads can be generated to allow applications such as RNA-seq or flow cytometry.

Taking biomanufacturing in house

Historically, strain development for applied markets was largely undertaken by academics, biofoundries and private companies – similar to the CRO approach used by the pharma sector – who would engineer and optimize strains for sale to end users. Following this upstream processing, manufacturers would then take the engineered strain and use it in scaled up biomanufacturing processes, helping them to move away from chemical synthesis and towards bio-based products. The increase in the use of biosubstitutes has driven a move towards in-house R&D, with manufacturers investing in scientific teams focused on strain development in microorganisms such as bacteria, fungi and algae. For many of these companies, in-house engineering of cell lines is a new venture, and partnering with an experienced NGS instrument and reagent supplier from the outset is hugely beneficial, allowing them to draw on years of experience in the field as they embark on this exciting new pathway.

Developing an upstream bioengineering workflow

The biomanufacturing process begins with strain engineering. The higher the complexity of the desired product, the higher the number of strains to be built and screened. Numerous iterations of the design-build-test-learn procedure are required until the right strain is obtained.

Genetic engineering, directed evolution or mutagenesis are applied to obtain the right strain. For genetic engineering or gene editing, the good combination of enzymes, oligos and assembly procedure is key. This requires fast, accurate dispensing of small volumes, and acoustic liquid handlers are ideal for this application, offering tip- and contact-free dispensing of nanoliter volumes with excellent precision and reproducibility.

The edited cells are then cultivated and analyzed, including plasmid NGS and gene expression analysis to confirm the correct gene insertion and functionality to create the desired end product. Typically, this is performed on an automated liquid handling platform with integrated modules – such as microplate readers, analyzers, and light cyclers for PCR reactions – using high-quality reagents designed specifically for genomic applications. Finally, once the best host has been established, strain production is optimized and scaled up. Microbioreactors are ideal for process optimization, enabling screening of the chosen best producing organism and determining the ideal growth medium, pH, and CO₂ conditions for maximum production.

Directed evolution – where an organism is encouraged to modify naturally – may also be used as an alternative to gene editing. In order to find the single strain producing the desired function, laboratories may use flow cytometry to sort the best producing bacteria one at a time.

The voice of experience

The support of an experienced supplier is essential for manufacturers venturing into strain engineering. Beckman Coulter Life Sciences has extensive expertise in biopharma, which translates perfectly to biomanufacturing applications in both biofoundries and companies developing their own strains. We can also provide complete solutions for each stage of the workflow, including cell culture, genomics, gene extraction and (CRISPR) editing, and NGS library preparation. We know that sustainability matters to our customers, and are committed to meeting our net zero commitments, working with our partners to minimize the use of plastic consumables in biomanufacturing workflows and helping them to confidently achieve their goal of substituting carbon sources with bioreplacements.

Contact us to find out more about how we can support your biomanufacturing processes.

References

1. https://www.genengnews.com/news/gauging-ngs-impact-on-biomanufacturing/