The quest for molecular quasi‐species in ligand‐activity space and its application to directed enzyme evolution

摘要

Weproposethattheproperevolvingunitinenzymeevolutionisnotasingle“fittestmolecule”,butaclusterofrelatedvariantsdenoteda“quasi‐species”.Adistributionofvariantsprovidesgeneticvariabilityandtherebyreducestheriskofinbreedingandevolutionarydead‐ends.Differentmatricesofsubstratesoractivitymodulatorswillleadtodifferentselectioncriteriaanddivergentevolutionarytrajectories.Weprovideexamplesfromourdirectedevolutionofglutathionetransferasesillustratingtheinterplaybetweenlibrariesofenzymevariantsandligandmatricesintheidentificationofquasi‐species.Theligandmatrixisshowntobecrucialtotheoutcomeofthesearchfornovelactivities.Inthissensetheexperimentalsystemresemblesthebiologicalenvironmentingoverningtheevolutionofenzymes...