Polylactic acid (PLA) is one of the most promising biodegradable materials. It has potential applications in disposable packaging, agriculture, medicine, and printing filaments for 3D printers. Current biosynthesis of PLA entirely uses edible biomass as feedstock.
Plastic pollution has become one of the most pressing environmental issues today, leading to an urgent need to develop biodegradable plastics1-3. Polylactic acid (PLA) is one of the most promising biodegradable materials because of its potential applications in disposable packaging, agriculture, medicine, and printing filaments for 3D printers4-6. However, current biosynthesis of PLA entirely uses edible biomass as feedstock, which leads to competition for resources between material production and food supply7,8. Meanwhile, excessive emission of CO2 that is the most abundant carbon source aggravates global warming, and climate instability. Herein, we first developed a cyanobacterial cell factory for the de novo biosynthesis of PLA directly from CO2, using a combinational strategy of metabolic engineering and high-density cultivation (HDC). Firstly, the heterologous pathway for PLA production, which involves engineered D-lactic dehydrogenase (LDH), propionate CoA-transferase (PCT), and polyhydroxyalkanoate (PHA) synthase, was introduced into Synechococcus elongatus PCC7942. Subsequently, different metabolic engineering strategies, including pathway debottlenecking, acetyl-CoA self-circulation, and carbon-flux redirection, were systematically applied, resulting in approximately 19-fold increase to 15 mg/g dry cell weight (DCW) PLA compared to the control. In addition, HDC increased cell density by 10-fold. Finally, the PLA titer of 108 mg/L (corresponding to 23 mg/g DCW) was obtained, approximately 270 times higher than that obtained from the initially constructed strain. Moreover, molecular weight (Mw, 62.5 kDa; Mn, 32.8 kDa) of PLA produced by this strategy was among the highest reported levels. This study sheds a bright light on the prospects of plastic production from CO2 using cyanobacterial cell factories.