Kurzbeschreibung
(Englisch)
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Although proteins are genetically encoded, the activity of metalloproteins (and their genetic de-scendants) crucially depends on metal availability. Consequently, metalloproteins are a useful model from the emerging field of “molecular environomics”, defined as the study of the adaptation (and evolution) of a system according to environmental conditions. Here, we explore the environmental adaptation of a bacterial enzyme (dapE) with two curiously independent activities in vivo according to the nature of catalytic metal bound: a manganese-dependent peptidase activity and a zinc-dependent desuccinylase activity. We implement a plat-form for directed evolution towards these two separate activities with different metals, with the aim of producing a model of how bacteria and metallohydrolases adapt to metal-availability and toxic-ity over laboratory-evolution time-scales. The project is designed for a postdoctoral worker for 18 months using techniques that are now well established in the Creus laboratory and offers ample opportunity for integration and collabo-ration within the COST network. The outcome of the project will be a more detailed description of how protein evolution adapts to metal cation-availability and toxicity, an important question with implications in biomedicine and in bioremediation.
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Partner und Internationale Organisationen
(Englisch)
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AT, CH, CZ, DE, DK, EL, ES, FI, FR, HU, IE, IL, IT, LV, PL, PT, SE, SK, TR, UK
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Abstract
(Englisch)
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The project explored the emerging field of “molecular environomics”, defined as the study of the adaptation and evolution of a system at the molecular level according to environmental conditions. Here, we explored the environmental adaptation of a bacterial enzyme (dapE) -a potential antibiotic drug target- with two curiously independent activities in vivo according to the nature of catalytic metal bound: a manganese-dependent peptidase activity and a zinc-dependent desuccinylase activity. We implemented a platform for laboratory directed evolution towards these two separate activities with different metals, with the aim of producing a model of how bacteria and metallohydrolases adapt to metal-availability and toxicity over laboratory-evolution time-scales. The outcome of the project was a more detailed description of how protein evolution adapts to metal cation-availability and toxicity, an important question with fundamental implications in evolution and practical use in drug discovery.
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