In the last few years, the life science sector has been taken by storm by what I like to call the “synthetic biology revolution”. Some believe synthetic biology is just a cooler and catchier way of referring to molecular biology/genetic engineering, others support the idea of it being a new and exciting discipline with a huge potential of driving innovation as well as creating business opportunities/value in different sectors such as agriculture, energy, and healthcare. I definitely fall into the latter category. During my Master’s dissertation at Cambridge University, I explored the commercial potential associated with applying synthetic biology to the manufacture of small molecule drugs with the idea of understanding where the opportunities and challenges lie.
Leveraging synthetic biology techniques could be advantageous.
“Small molecule drug manufacture” is a broad and diversified area of the Pharma world as different types of drugs are made in different ways, with the synthetic chemistry being the most common. The innovative synthetic biology approach has already been shown to be technologically advantageous, for instance by the famous example of Jay Keasling’s work on the anti-malarial agent artemisinin. Interestingly, synthetic biology seems to be suited for the manufacture of certain molecules rather than others. There are some difficulties or rather some characteristics of small molecule drugs that, when it comes to the process of manufacturing, really resonate with the concept of replacing the old, traditional synthetic chemistry route with a SynBio-based route. The presence of several chiral centres and a general structural complexity in some molecules represent a significant hurdle for standard medicinal chemistry. However, they could potentially be overcome by developing synthetic biology-based production systems. Again, molecular features that fit the synthetic biology concept are “natural occurrences”, as enzymes that catalyse for the required synthetic steps already exist in nature, and modularity of biosynthetic pathway which can be leveraged when engineering the living system for the production of those drugs.
Based on these features, the molecular classes of small molecule drugs that could, at first glance, benefit the most from a SynBio approach include polyketides, alkaloids, and carboxylic acid derivatives (such as non-ribosomal peptides).
A future synthetic biology approach to drug manufacture would not only be beneficial from a technical perspective but would also satisfy drivers that in turn motivate the pharmaceutical industry’s movement towards its adoption.
What are the drivers that underlie a possible shift towards SynBio?
The most straight-forward reason to apply synthetic biology to drug manufacture is the reduction of manufacturing costs (related to cost of reagents, low yields, cost of starting materials, racemic synthesis and number of synthetic steps (each entailing specific conditions therefore costs). Secondly, synthetic biology could make the process more sustainable from an environmental perspective, for instance by getting rid of heavy metal catalysts or dangerous reagents currently used routinely in drug manufacture. A third driver could be becoming able to meet synthesis requirements for chemical development, hence have the capacity to rescue drug candidates which are challenging to produce and would otherwise get discontinued despite being very interesting from a bioactivity point of view.
Easier said than done: challenges that mark the path to adoption.
Unfortunately, even though several potential drivers underlie the benefits of adoption of synthetic biology to drug manufacture, and some compound classes clearly seem to necessitate a “synbio revolution”, the path to adoption by the industry is ridden with challenges.
Just to mention a few obstacles, it is very difficult (however not impossible) that pharma companies will consider changing manufacturing processes for established drugs, because such a change would face regulatory barriers, such as repeating toxicology examinations and impurity profiling with associated costs to demonstrate the final product is the same. Therefore it seems that the technology could be exploited more easily for new developments rather than for the improvement of already-on-the-market drugs.
Furthermore, a barrier to adoption by the industry is the fact that the power of synthetic biology as a ground-breaking tool is not yet fully proven, therefore companies are still somewhat ambivalent towards the technology.
Nevertheless, despite obstacles, it is obvious that there is some excitement and synthetic biology will be hopefully having a huge impact in the near future on drug manufacturing as well as a number of other fields in the life science arena. I’d like to believe that we are witnessing a revolution in the making.