Fuzhong Zhang1

1, Energy, Environmental & Chemical Engineering, Washington University, Saint Louis, Missouri, United States

Advances in synthetic biology have enabled the quantitative engineering of dynamic biological processes for the precise control of cellular reaction networks, allowing engineered cells to perform complex tasks and to produce various small molecules, which can be used as biofuel replacements, polymer precursors, nutraceuticals, and pharmaceuticals. Compared to small molecules, the production of macromolecular biomaterials by synthetic biology approaches is strongly lagging. Nature has evolved various types of protein materials with remarkable mechanical properties and functions. To facilitate the practical use of these materials, we aim to engineer bacterial cell factories to overproduce high-performance protein-based materials, such as spider silks. We have developed synthetic biology strategies that allow us to synthesize ultra-high molecular weight spidroins (556 kDa) at gram per liter scales. Fibers spun from our microbially produced spidroin fully replicate the mechanical performance of natural spider silk by all common metrics, i.e. tensile strength (1.03 ± 0.11 GPa), modulus (13.7 ± 3.0 GPa), extensibility (18 ± 6%), and toughness (114 ± 51 MJ/m3). The developed strategy reveals a path to more dependable production of high-performance silks for mechanically-demanding applications while also providing a platform to facilitate production of other high-performance natural materials.