Synthetic Biology Symposium

The Jackson lab attended the CSIRO Synthetic Biology Cutting Edge Symposium, which was hosted by CSIRO and Synthetic Biology Australasia in Canberra this week. Colin gave a talk at the session on ex vivo synthetic biology and Jason won a prize for his poster “SERIOS investigations of synaptic plasticity”. Congratulations Jason!

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New publication

Congratulations to Nick, Peter, and Galen, whose paper “Evolution of protein quaternary structure in response to selective pressure for increased thermostability” has been published in JMB.

This paper shows that when directed evolution was used to impose selective pressure for increased thermostability in an insect carboxylesterase, stabilization was achieved by enrichment of more stable oligomeric species. This result supports the hypothesis that oligomerization is one possible evolutionary strategy for improving protein thermostability.

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New publication

Congratulations to Peter, Galen and Nick, whose paper “Conformational disorganization within the active site of a recently evolved organophosphate hydrolase limits its catalytic efficiency” was published in Biochemistry.

In this paper, we characterised a gain-of-function substitution in an enzyme, which provides resistance to organophosphate pesticides in the Australian sheep blowfly. The full catalytic potential of this substitution is not realised because of frequent sampling of conformational states that are unproductive for catalysis. This may be a common feature of recently-evolved enzymes.

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New publication

Congratulations to Hafna and Elaaf, whose paper “Protonation state of F420H2 in the prodrug-activating deazaflavin dependent nitroreductase (Ddn) from Mycobacterium tuberculosis” was published in Molecular BioSystems.

We identified the protonation state of the cofactor of Ddn, which is important for understanding the mechanism by which this enzyme activates anti-mycobacterial prodrugs.

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New publication

Congratulations to Ben, whose paper “Ancestral protein reconstruction yields insights into adaptive evolution of binding specificity in solute-binding proteins” has been published in Cell Chemical Biology.

This paper gives a new structural and thermodynamic perspective on the evolution of binding specificity and shows the role of conformational plasticity and enthalpic interactions for promiscuous binding in an ancestral solute-binding protein.

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New publication

Congratulations to Hafna and the rest of the FDOR team, whose paper “Sequence-structure-function classification of a catalytically diverse oxidoreductase superfamily in mycobacteria” has been published in JMB.

This reclassification, functional annotation and structural analysis of flavin/deazaflavin oxidoreductases (FDORs) shows the varied functions of FDORs in mycobacteria and provides a framework to understand their role in mycobacterial pathogenesis and persistence.

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New publication

Congratulations to Eleanor, who published a paper entitled “Reverse evolution leads to genotypic incompatibility despite functional and active site convergence” in eLife, together with our incredible collaborator Nobuhiko Tokuriki at the University of British Columbia.

This paper shows that the evolution of a enzyme in vitro can be reversed by reversing the selection pressure, but not by reversing the substitutions originally responsible for the change in function. This shows how epistasis can make evolution phenotypically reversible, but genotypically irreversible.