Synthetic biology strategies for synthesizing polyhydroxyalkanoates from unrelated carbon sources

Discovered in the 1920s, polyhydroxyalkanoates (PHA) are a naturally occurring class of biopolyesters that have long been touted as a renewable, biodegradable plastic alternative. Demand for sustainable products and over a half century of research have led to moderate commercial success of PHA. Yet, these materials are not pervasive. Therefore, an important question to address is, “what is the barrier that prevents widespread application of these materials?” PHA can be made from an incredibly diverse class of monomers that incorporate both simple and complex organic acids. Herein, we provide an updated list of unique PHA monomers that are substrates for a PHA polymerase. Unfortunately, most unique monomers are incorporated only after feeding a structurally related feedstock to a PHA accumulating bacterium. Therefore, we put forward an argument that research must now turn to developing feedstock-independent, synthetic pathways to produce an increased diversity of PHAs capable of competing with petroleum-derived plastics.