The Evolution of New Catalytic Mechanisms for Xenobiotic Hydrolysis in Bacterial Metalloenzymes

Abstract

An increasing number of bacterial metalloenzymes have been shown to catalyse the breakdown of xenobiotics in the environment, while others exhibit a variety of promiscuous xenobiotic-degrading activities. Several different evolutionary processes have allowed these enzymes to gain or enhance xenobiotic-degrading activity. In this review, we have surveyed the range of xenobiotic-degrading metalloenzymes, and discuss the molecular and catalytic basis for the development of new activities. We also highlight how our increased understanding of the natural evolution of xenobiotic-degrading metalloenzymes can be been applied to laboratory enzyme design.

Active Site Desolvation and Thermostability Trade-Offs in the Evolution of Catalytically Diverse Triazine Hydrolases

“…24 However, the selection pressure for xenobiotic-degrading enzymes is generally directed toward high turnover rates, 25−27 as the efficient breakdown of these compounds can directly impact organism survival. 28 Accordingly, the natural evolution of such enzymes is often rapid, and inefficient ancestral sequences are often inherently transient. This difficulty in isolating short-lived evolutionary intermediates restricts our understanding of enzyme catalysis to extant (and often very efficient) enzymes.…”

“…These effects are examples of ground state destabilization, , which is generally considered to contribute less to catalysis by highly efficient enzymes than transition state stabilization. , This is of course a simplified description, as many other factors can contribute to enzyme efficiency, and enzyme efficiency is not the only criteria required and selected for by nature . However, the selection pressure for xenobiotic-degrading enzymes is generally directed toward high turnover rates, − as the efficient breakdown of these compounds can directly impact organism survival . Accordingly, the natural evolution of such enzymes is often rapid, and inefficient ancestral sequences are often inherently transient.…”

Celebrating RACI and Academy of Science Awards

“…[4] Colin Jackson (ANU), winner of the Organic Division's 2015 Rennie Memorial Award, has presented a review with co-authors E. Sugrue, C. Hartley, and C. Scott on 'The Evolution of New Catalytic Mechanisms for Xenobiotic Hydrolysis in Bacterial Metalloenzymes'. [5] Lara Malins, formerly a Ph.D. student at the University of Sydney under Professor Richard Payne and now a post-doc at UC San Diego, won the RACI's 2015 Cornforth Award for the best Ph.D. thesis and has contributed a highlight on 'TransitionMetal Promoted Arylation: An Emerging Strategy for Protein Bioconjugation'. [6] Christopher Gordon Newton, the Organic Division's inaugural 2015 Mander awardee for the Best PhD Thesis in Organic Chemistry, then a student in Professor Michael Sherburn's group and now a post-doc at the EPF Lausanne, has contributed a review together with E. G. Mackay on 'Masked Ketenes as Dienophiles in the Diels-Alder Reaction'.…”