Synthetic Biology and Natural Products

Our society urgently requires a transition from fossil fuel dependence to a biosustainable economy. Petroleum-based chemical synthesis is critical for fueling societal development, producing more than 100,000 industrial molecules and a market size of 2 trillion USD, but it also accounts for 20% of global industrial CO₂ emissions. Scientists have long dreamed of replacing petrochemical synthesis with biomanufacturing. However, most petrochemicals for daily use are new-to-nature molecules without any natural biosynthetic route, so establishing a biomanufacturing platform capable of biosynthesizing large numbers of new-to-nature molecules is key to our success.

Modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) are megasynthases that produce complex natural product pharmaceuticals in an assembly-line manner. Within each functional module, the chemical structure of the product is strictly determined by the order of each enzymatic domain; one such megasynthase can incorporate hundreds of domains, leading to a vast chemical design space. Because of this, scientists envisioned designing PKS/NRPS systems to replace petroleum-based chemical synthesis and produce nearly any organic molecule. However, this vision has seen limited success due to the lack of harnessed engineering tools, enzymes and chassis strains.

Through establishment of such retrobiosynthetic platforms integrated with an automated computational design network, I aim to produce a broad spectrum of specialty and commodity chemicals (pharmaceuticals, cosmetics, food additives, etc.) in harnessed chassis strains, bridging the gaps in the implementation of biomanufacturing with a projected 50 billion USD market size in 2035, and ultimately contributing to building a more sustainable and greener future.