Combinatorial metabolic engineering platform enabling stable overproduction of lycopene from carbon dioxide by cyanobacteria

摘要: Cyanobacteria are simple, efficient, genetically-tractable photosynthetic microorganisms representing ideal biocatalysts for CO2 capture and conversion, in principle. In practice, genetic instability low productivity key, linked problems engineered cyanobacteria. We took a massively parallel approach, generating characterising libraries of synthetic promoters RBSs the cyanobacterium Synechocystis, assembling sparse combinatorial library millions metabolic pathway-encoding construct variants. Laboratory evolution suppressed variants causing burden leading to expected instability. Surprisingly however, single round without iterative optimisation, 80% chosen at random overproduced valuable terpenoid lycopene from atmospheric over many generations, apparently overcoming trade-off between stability productivity. This first large-scale engineering cyanobacteria provides new platform development genetically stable cyanobacterial sustainable light-driven production products directly CO2, avoiding fossil carbon or competition with food production.