2024 AIChE Annual Meeting
Optimizing Polyhydroxyalkanoate Production: Computational Design and Engineering of Phac for Enhanced Biodegradable Plastics
PhaC is a critical enzyme for synthesizing polyhydroxyalkanoates (PHAs), biodegradable polymers from renewable resources that offer an eco-friendly alternative to petroleum-based plastics. PhaC has been effectively utilized in microbial systems to produce PHAs, with Cupriavidus necator being a particularly promising host for such applications. A novel potential application for PHAs is in crewed Mars missions, where they could provide regenerative bioplastics for material manufacturing in situ. However, to generate durable, high-performance plastics, it is necessary to optimize substrate-binding and increase substrate breadth of PhaC. This study advanced this goal by developing a PhaC mutant library through epPCR, coevolutionary analysis of protein sequences, and MutComput, a neural network algorithm. This effort led to the identification of 124 promising sites and the creation of a mutant library of several hundred thousand members. Molecular visualization tools revealed that these sites lie within critical protein domains, such as substrate-binding domains and plastic egress channels.