From Niche to Transformational: Using Biology for Chemistry in Pharmaceutical Development

Though synthetic biology may be regarded as a new or emerging field of science, the concept of applying biological systems to improve chemical synthesis goes back hundreds — arguably, thousands — of years. From the earliest fermentation processes yielding beer, wine, and leavened bread to the discovery, development, and production of life-saving therapeutics of many types, biocatalysis and biosynthesis has had a profound impact on the chemistry that animates life.

In the pharmaceutical realm, these modern molecular biology tools have the potential to substantially enhance the efficiency, scalability, and sustainability of drug development. Fermentation and biocatalysis approaches have already been long proven to yield commercially viable processes – everything from bulk commodities to fine chemicals to complex pharmaceuticals. With advances in molecular biology, applications of biocatalysis and synthetic biology are poised at an inflection point – useful niche technology and transformative science.

Evolution of Biocatalysis in Chemical Synthesis

Like many facets of research science, precise definitions of synthetic biology can vary by discipline and application. In this context, we are broadly referring to the manipulation and application of biological catalysts and systems for chemical synthesis.

While it is clear that biocatalysis has played a significant role in organic chemistry throughout history, the inherent structural and functional complexity of biological catalysts as compared to their chemical counterparts has largely prioritized the rational development of “classic” synthetic chemistry as the dominant science.

These biocatalysts have evolved considerably over evolutionary time for their function, however recent advancements in technology may both facilitate and hinder their practical use. For example, the high selectivity of biocatalysts may offer process efficiency and purity benefits, but their limited synthetic range may present challenges for chemists seeking a predictable, streamlined reagent option.

Innovation Accelerating the Potential of Biocatalysis in Pharmaceutical Development

A substantial convergence of technical innovations – coupled with our ‘inheritance’ of the machinery of natural evolution – has provided a powerful mechanism for chemists to overcome historical limitations of biocatalysts and harness their intrinsic strengths. A few of these noteworthy technical advancements are summarized below. In combination with our accumulated practical knowledge for effective bioprocess development, they are promising to translate biocatalysis and synthetic biology tools into practical, scalable, and effective chemical processes.

• Acceleration of genomics. A broader array of functional genes being identified has enabled faster sequencing of genetic information, as well as and synthesis and engineering of genes of interest.
• Availability of bioinformatic data. The rapid, exponential growth of bioinformatic databases containing gene sequences for a wide variety of enzymes with known functions has made it easier for biologists and synthetic chemists alike to locate enzymes capable of doing almost any chemistry.
• Advancements in molecular biology technology. Molecular biology tools for editing genes as well as the instructions for producing active and stable proteins continue to improve.
• Directed evolution and efficient enzyme engineering. Mechanisms for engineering or further evolving biocatalysts are making it possible for chemists to tailor processes to their specific needs and goals, offering significant potential in reducing pharmaceutical development timelines and dramatically improve performance and fit for purpose.
• High-throughput screening infrastructure. The efficient microscale screening of enzymes for their reactions with small molecules can serve to accelerate synthesis and medicinal chemistry analoging efforts.
• Molecular modeling. A wide variety of analytical and -omics tools allow chemists to better and more quickly understand how to engineer complex molecules.
• Artificial intelligence. The evolution of effective algorithms, computational techniques, and artificial intelligence are continuously improving molecular design capabilities, expanding our understanding of these structurally complex catalysts and how they can be usefully modified.

Practical Applications of Biocatalysis & Synthetic Biology in API Development

Nature has evolved the capacity to design, synthesize, and recycle the spectacular array of chemical structure diversity that allows life to exist, function, and constantly adapt. Every living cell utilizes available starting materials (nutrients) to cleanly and efficiently synthesize the full diversity of biologically-active molecules – safely and with minimal waste – under mild and uniform reaction conditions that exist around the cell.

Ultimately, advancements in synthetic biology are enabling bench researchers to access once unimaginable aspects of biosynthetic capabilities, making it possible to tailor biological catalysts to individual process goals and perform complex chemistries under mild and uniform conditions.

For more on the role of these technologies in process development, including key regulatory considerations and detailed, practical examples of landmark industrial applications, we invite you to access our full webinar, “Translating Molecular Biology Technologies into Practical Processes for API Production.”