Significant technical innovations are needed to improve the economics of plastic recycling. Plastic recycling rates in the United States have been stagnant for more than a decade: less than 10% of plastics are currently recycled, and the remainder are incinerated (15%) or landfilled (75%). Plastic is being consumed at an unsustainable rate, representing a significant economic and environmental cost to the United States. Plastics have become a major contributor to global warming, as emissions from global plastics production and incineration could reach 56 billion tons of carbon between now and 2050, accounting for 15% of the global greenhouse gas emissions. The economics of conventional plastic recycling are poor, as high temperatures are frequently used to recycle plastics, resulting in degradation of plastic quality and other quality issues that greatly reduce the economic value of recycled plastics. This proposal will apply synthetic biology and related biotechnologies to design, engineer, and optimize new enzymes and enzyme cocktails to break down plastic waste for recycling and upcycling into new, high-value plastic products using an efficient, cost-effective, closed-loop recycling system. Naturally occurring polyurethanase enzymes target polyurethane products such as packaging foams and building insulation, which typically take years or decades to completely degrade. Polyurethanase enzymes will be engineered to improve their speed and ability to target and cut polyurethane polymers under scalable process conditions. Millions of enzyme variants will be constructed, tested, and analysed using synthetic biology, high-throughput screening, and machine learning technologies. Phase I of this proposal focuses on developing high performance enzymes for polyurethane recycling that improves recycling rates of a complex mix of polyurethane products by 100-fold. Phase II of this proposal will focus on additional enzyme improvements, as well as development of a low-cost bioprocess to ensure efficient recovery and yield of high quality recycled polyurethane building blocks from consumer and industrial products. The 2020 market for plastic recycling is $1.7 billion in the United States and $26.5 billion globally, with compound annual growth rates of 4.1% and 5.4%, respectively. High-performance engineered enzymes and bioprocess technology will accelerate growth of this industry and mitigate the unsustainable manufacture of virgin plastics from oil and gas, including the downstream landfilling of plastics with their associated environmental contamination and carbon emissions. Improved economics of plastic recycling will motivate materials recovery facilities to invest in plastic recycling infrastructure, as enzyme-mediated plastic recycling could save millions of dollars in shipping and dumping fees. Globally, up to $60B in economic value could be generated each year by improved recovery and recycling of plastic products. Societal and environmental benefits resulting from reductions in oil consumption and carbon emissions will accelerate as these technologies are implemented. Importantly, market growth will be spurred by governmental policies designed to encourage efficient, closed-loop plastic recycling, such as national taxation of carbon emissions, state requirements for minimum recycled plastic content in packaging and other materials, and producer responsibilities for the fate of plastic products.