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 its enzymatic domains. A single megasynthase can contain hundreds of domains, creating a vast chemical design space. We envision engineering PKS/NRPS systems to replace petroleum-based chemical synthesis and enable the production of virtually any organic molecule. By establishing such retrobiosynthetic platforms integrated with automated computational design frameworks, we aim to produce a broad spectrum of specialty and commodity chemicals in engineered host microorganisms.