Improvements in net titre achieved with microbial production are needed to meet growing demand for high-quality bioproducts. Net titre refers to the yield per litre of fermentation plant after the losses associated with downstream processing have been deducted.
Fortunately, more sustainable and efficient bioprocessing methods powered by innovative technology can balance impressive initial titres with the loss of material incurred during purification, addressing the practical and economic realities of overall yield.
High titre can be misleading
High titres are frequently showcased as a measure of a bioprocess’s productivity. However, because these figures don’t account for losses during Down Stream Processing (DSP) (such as removing host cell proteins, post-translational modifications and improper folding), in which significant yield reductions can occur, they don’t accurately reflect profitability and project viability.
Downstream processing impacts efficiency
Traditional bioprocessing methods focus on optimising expression systems to achieve high titres, often using host cells like CHO or Pichia pastoris. While these methods can achieve high initial titres, they frequently fall short in terms of net yield due to loss of material during complex purification processes, leading to increased costs, and reduced overall efficiency.
An integrated approach to maximise net titre
A more holistic approach is to optimise the genetic and metabolic pathways of the host cells to maximise titre, while also refining downstream processes to minimise product loss.
Techniques using quantitative trait loci (QTL) technology and advanced synthetic biology can be employed to create robust strains with improved traits that enhance both production and purification efficiency. This integrated strategy ensures that high titres translate into high net yields, making the process commercially viable and sustainable.
Higher yields and lower costs
Aside from reducing the gap between gross and net titre, lowering production costs, and increasing yield, this integrated approach also addresses DSP challenges upfront, ensuring a smoother transition from lab-scale to industrial-scale production. Furthermore, it provides a versatile solution for the bioprocessing industry that can be applied to various bioproducts, such as pharmaceuticals and biofuels.
Proven results and future potential
Recent studies (Baumann & Hubbuch, 2017) show that integrating DSP optimisation with upstream processes can lead to substantial improvements in net yield. For instance, advancements in host cell engineering and purification techniques have demonstrated increased net titres in biopharmaceutical production. A case study (Pan et al, 2022) involving the production of a therapeutic protein using Pichia pastoris revealed that optimising both expression and purification steps resulted in a 30% increase in net yield compared to traditional methods.
Integration as standard
In the coming years, achieving efficient and cost-effective bioproduction will depend on integrating upstream and downstream processes. Innovation in synthetic biology and DSP technologies will play an important role in enhancing bioprocessing scalability and sustainability to meet the growing demand for high-quality bioproducts. However, understanding the specific basis of the form of synthetic biology being used is critical. This is where QTL technology differentiates from existing synthetic biology, which is subject to the limitations associated with a defined genetic chassis adjusted by genetic engineering.
