Beauty companies have identified specific peptides with substantial potential as active ingredients in cosmetics, cosmeceuticals, and other consumer products. However, manufacturing such peptides at scale, and at a cost that meets the cost of goods for their industry, while still achieving the high quality required, remains a barrier to realising their commercial potential.
One possible solution often considered is the recombinant manufacture of such peptides using E. coli. Recombinant manufacture has many attractive aspects, but before using E. coli as the expression host, a rigorous, evidence-based feasibility assessment is advised.
E. coli as a manufacturing host
As a bacterium, E. coli is a prokaryote, meaning it has no cell nucleus. The gene relevant to the peptide of interest is usually inserted into the E. coli cell on a plasmid vector.
For some peptides, this leads to E. coli becoming an attractive means of manufacture that can match the cost requirements of beauty industry ingredients. However, to avoid wasted resources and project failure, it is important to understand which peptides are feasible for manufacture with E. coli and what the potential issues and restrictions might be.
As the beauty industry seeks to harness the potential of biotechnology to create products with new capabilities aligned to their customers’ unmet wishes, the role of peptide ingredients is set to become more important. However, the realities of biology mean the attributes of peptides necessary to deliver the impact on skin and hair that consumers are seeking may frequently exceed what E. coli can deliver.
Unsuitable Peptides
E. coli lacks much of the machinery of eukaryotic cells (cells with a nucleus) which significantly limits the nature of the peptides they can generate. Post-translational modifications to the peptide are largely impossible with E. coli and such modifications are becoming increasingly essential for the targeted bioactivity and/or stability of the peptide.
For example, E. coli has limited capability to achieve the specific folding needed for many peptides, which is frequently essential for their targeted bioactivity. It typically lacks the chaperone proteins needed and is largely incapable of making disulphide bonds needed to stabilise and correctly fold peptides. E. coli also lacks eukaryotic secretion machinery, so most recombinant peptides of value cannot penetrate the outer membrane and need to be extracted by complex methods, breaking the cells open, leading to impurity issues.
If the E. coli cells are lysed to recover the peptides, this increases the issue of toxic bacterial host cell components, such as fever-causing “pyrogens,” which are difficult to remove from the peptides before they are added to consumer products. Additionally, peptides are often degraded by native proteases, meaning that only a small fraction of the total peptides produced can be recovered.
Complications with E. coli manufacture
As well as restrictions on the type of peptide that E. coli can generate, there are also issues with the actual mechanisms by which they operate, which undermine their feasibility in scaled recombinant manufacture of certain peptides. These include:
- Short peptides, under 50 amino acids long, are vulnerable to complete degradation by E. coli proteases.
- Peptides tend to accumulate in an insoluble form, leading to aggregation and inclusion body formation that requires subsequent complex refolding protocols that are inefficient, reduce yield and drive up the cost of manufacture.
- Some peptides, especially antimicrobial or cytotoxic peptides, can be toxic to E. coli, because it is a microbe, thereby reducing cell growth and productivity.
- For many peptides with valuable properties, especially hydrophobic or highly charged sequences, achieving high expression levels can be challenging.
Technical solutions can be created for some of the above, but they are no guarantee of success and add up-front expenditure, risk, time and ongoing cost of goods. Such solutions cannot address the limitations for those peptides that are unsuitable for E. coli manufacture.
Biotechnology solutions for an evolving beauty industry
The entry of biotechnology into the beauty industry opens the door for more effective peptide ingredients. However, the bioactivity of a peptide often requires more than just the primary chemical structure, but also the correct post-translational modification/folding.
At present, marketing of peptide containing products frequently focuses on the presence of a peptide in the ingredient list. However, audiences are getting ever more sophisticated and discerning in the scrutiny of the products they are buying.
The evidence supporting the claims made for peptide ingredients and the final products that contain them is improving, demonstrating the difference between peptides that are effective and those with unvalidated claims.
This is when the details of the peptides, such as their exact chemical make-up, conformational shape, charge distribution, and post-translational modification, will, in many cases, become critical. Only those versions of a given peptide with the correct attributes will deliver the bioactivity necessary to give consumers the benefit they are seeking. High-quality versions of such peptides that have been proven to deliver the desired effect under rigorous objective scientific testing will become premium and distinct from versions that cannot meet this benchmark.
Conclusion
Recombinant manufacturing offers many advantages for peptide ingredients in the beauty industry, including consistent high-quality, scalability, and lower production costs. These attributes are likely to become increasingly important as skincare and haircare products emerge, providing new benefits that match customers’ aspirations.
E. coli will undoubtedly play a role in this product evolution, but the limitations of this host cell will restrict it to a limited range of peptides. Alternative microbial hosts, especially well-characterised and safe eukaryotes such as Saccharomyces cerevisiae, are set to outperform E. coli when more complex peptides are needed with the desired biological activity. Importantly, these can now be developed using QTL technology, which harnesses evolutionary genomics to adjust the whole genome for the peptide concerned. This offers the ability to get high titre and low cost of goods for both complex and simple peptides, while ensuring a consistent match to the specific requirements for bioactivity needed for each consumer product.
