Seminars

As pollution from single-use petrochemical plastics continues to worsen, there is an urgent need to find alternative materials. Polyhydroxyalkanoate (PHA) is a promising alternative material that can be produced from renewable plant oils, is biodegradable, and possessed properties like those of commodity plastics. PHA synthase (PhaC) is the key enzyme in PHA biosynthesis, but the exact catalytic mechanism has remained elusive. In this seminar, I will present crystal structures of PhaC in various conformations, including the open and closed forms. Structural comparison of PhaC identified a dynamic region called the LID region, which regulates the opening of the substrate entry pathway. The LID region must be restructured during catalysis to allow substrate entry into the catalytic site. The structure of CoA (Coenzyme A)-bound PhaC heterodimer shows that one protomer adopts an open conformation when bound to CoA, while the other protomer adopts a closed conformation without CoA. This open-closed heterodimer indicates the open conformation is stabilized by the asymmetric dimerization, enabling PhaC to accommodate CoA. Structural analysis of PhaC has identified mutation hotspots that improve its catalytic activity. I will also discuss the biochemical and enzymatic analyses of PhaC. These results provide a fundamental understanding on PhaC catalytic machinery and suggest potential regions for PhaC engineering to broaden substrate specificity. This seminar also discusses the future research on PHA biosynthesis and enzymatic plastic degradation in tackling the plastic pollution crisis.