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Background  Fatty alcohols are widely used in industrial chemicals. The biosynthetic pathways for fatty alcohols are diverse and widely existing in nature. They display a high capacity to produce fatty alcohols by the metabolic engineering of different microbe hosts. Direct recycling of carbon dioxide to fatty alcohols can be achieved by introducing a fatty alcohol-producing pathway into photosynthetic cyanobacteria. According to our precious reports, a relatively low yield of fatty alcohols was obtained in the genetically engineered cyanobacterium  Synechocystis  sp. PCC 6803.    Results  The photosynthetic production of fatty alcohols in  Synechocystis  sp. PCC 6803 was improved through heterologously expressing fatty acyl-Coenzyme A (acyl-CoA) reductase gene  maqu_2220  from the marine bacterium  Marinobacter aquaeolei  VT8. Maqu_2220 has been proved to catalyze both the four-electron reduction of fatty acyl-CoA or acyl-Acyl Carrier Protein (acyl-ACP) and the two-electron reduction of fatty aldehyde to fatty alcohol. The knockout of the aldehyde-deformylating oxygenase gene ( sll0208 ) efficiently blocked the hydrocarbon accumulation and redirected the carbon flux into the fatty alcohol-producing pathway. By knocking-out both  sll0208  and  sll0209  (encoding an acyl-ACP reductase), the productivity of fatty alcohols was further increased to 2.87 mg/g dry weight.    Conclusions  The highest yield of fatty alcohols was achieved in cyanobacteria by expressing the prokaryotic fatty acyl-CoA reductase Maqu_2220 and knocking-out the two key genes ( sll0208  and  sll0209 ) that are involved in the alka(e)ne biosynthesis pathway. Maqu_2220 was demonstrated as a robust enzyme for producing fatty alcohols in cyanobacteria. The production of fatty alcohols could be significantly increased by blocking the hydrocarbon biosynthesis pathway.

Improved production of fatty alcohols in cyanobacteria by metabolic engineering