How Genomics and Synthetic Biology Are Reopening Natural Molecule Drug Discovery

Speaking with BioPharm International®, Guillaume Vandenesch, CEO and co-founder of Generare, a Paris-based techbio company, discusses how 2 converging technologies are reopening natural product drug discovery. He also defines what distinguishes genuine tech bio companies from those that apply the label more loosely.

Vandenesch notes that natural molecules have played a foundational role in pharmaceutical history, considering that many major pharmaceutical companies were built on nature-derived compounds. However, he emphasizes, the modality was largely abandoned by the industry not because its potential was exhausted but because the enabling tools were no longer available. He stresses that an estimated 97% of natural molecular diversity remains unexplored.

How are genomics and synthetic biology converging to make natural product drug discovery scalable and competitive?

Vandenesch identifies 2 technologies whose recent maturation has made natural molecule discovery viable again at scale. First, genomics now enables the sequencing of hundreds of thousands of microbial and fungal genomes efficiently and at low cost. Second, synthetic biology and molecular biology tools allow scientists to manipulate DNA, enabling them to copy and transfer the biosynthetic blueprints of natural products encoded in bacterial and fungal genomes. Generare, Vandenesch explains, combines both approaches to access and characterize this previously inaccessible chemical space.

On the definition of tech bio, Vandenesch says the term is used inconsistently across the industry but states that its core value lies in creating virtuous cycles of learning, in other words, iterative loops in which computational prediction and experimental validation reinforce each other with each cycle.

"Each time you do this cycle, each time you get better at predicting the activity of your molecule," he says.

He describes this feedback loop, from gene prediction to molecule synthesis to biological activity testing and back, as the defining mechanism by which tech bio companies generate compounding value within the pharmaceutical ecosystem.

Explore more of the work that Generare is doing.

About the speaker

Guillaume Vandenesch, CEO and Co-Founder, Generare

Vandenesch leads Generare, a Paris-based techbio company generating novel, high-quality molecular data for drug discovery. A biotech engineer trained at AgroParisTech, he spent more than 15 years in deep tech, notably helping scale Hello Tomorrow into a global platform for breakthrough science, and leading an innovation studio to its acquisition by Capgemini Invent. In 2023, he co-founded Generare to address a key bottleneck in drug discovery: access to genuinely new molecular data.