Thawing out frozen metabolic accidents.

Photosynthesis and nitrogen fixation became evolutionarily immutable as "frozen metabolic accidents" because multiple interactions between the proteins and protein complexes involved led to their co-evolution in modules. This has impeded their adaptation to an oxidizing atmosphere, and reconfiguration now requires modification or replacement of whole modules, using either natural modules from exotic species or non-natural proteins with similar interaction potential. Ultimately, the relevant complexes might be reconstructed (almost) from scratch, starting either from appropriate precursor processes or by designing alternative pathways. These approaches will require advances in synthetic biology, laboratory evolution, and a better understanding of module functions.