Direct Conversion of CO₂ to α-Farnesene Using Metabolically Engineered Synechococcus elongatus PCC 7942

Direct conversion of carbon dioxide (CO₂) to value-added chemicals by engineering of cyanobacteria has received attention as a sustainable strategy in food and chemical industries. Herein, Synechococcus elongatus PCC 7942, a model cyanobacterium, was engineered to produce α-farnesene from CO₂. As a result of the lack of farnesene synthase (FS) activity in the wild-type cyanobacterium, we metabolically engineered S. elongatus PCC 7942 to express heterologous FS from either Norway spruce or apple fruit, resulting in detectable peaks of α-farnesene. To enhance α-farnesene production, an optimized methylerythritol phosphate (MEP) pathway was introduced in the farnesene-producing strain to supply farnesyl diphosphate. Subsequent cyanobacterial culture with a dodecane overlay resulted in photosynthetic production of α-farnesene (4.6 ± 0.4 mg/L in 7 days) from CO₂. To the best of our knowledge, this is the first report of the photosynthetic production of α-farnesene from CO₂ in the unicellular cyanobacterium S. elongatus PCC 7942.