Technoeconomic and Environmental Assessment of Enzyme-based Low-Phenylalanine protein for Phenylketonuria

This study presents a techno-economic and life cycle analysis of an enzyme-driven process for producing an affordable and sustainable low-phenylalanine protein supplement from crude protein. This method leverages immobilized Phenylalanine ammonia lyase (PAL) to produce alternative options to the amino-acid-based protein supplements that are currently available. Here, we have optimized the binding and conversion efficiency of bioconjugate to catalyse deamination of bulk phenylalanine present in protein hydrolysate. The scale-up was optimized and further simulated to produce 200 metric tons of processed protein annually for the management of Phenylketonuria (PKU). This scale-up was modeled using the scale-down data from 3, 14, and 50 L volumes. Our analysis indicated that performing enzyme production in a 5000 L bioreactor reduced enzyme costs by 57.5% compared to smaller scales, achieving a total production cost of $1.47/kg of low-Phe protein. Almost 69% of the total cost is attributed to raw materials, with the procurement of crude protein and Tris-Cl buffer being the major expense drivers. The Life Cycle Assessment (LCA) results demonstrated significant environmental trade-offs: the enzymatic route reduced greenhouse gas emissions by 40% compared to synthetic amino acid blends but incurred higher land and water use due to agricultural inputs and fermentation. This study confirms the strategic rationale, emphasizing scale optimization and enzyme recycling for cost-effective, high-volume therapeutic protein formulations for patients with PKU. • Scale-up to 5,000 L cuts cost by 57.5%, to $1.47/kg low phenylalanine protein • Immobilized phenylalanine ammonia lyase shows 10-fold higher conversion • Enzyme-based phenylketonuria supplement cuts greenhouse gases by about 40 percent • Low-cost $1.47/kg protein may improve phenylketonuria diet adherence