Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Building on a century of enzymology research and new genome-wide insights into enzyme families, increased interdisciplinary communication and a broad vision will advance our understanding of biological catalysts and enhance our ability to manipulate them.
The scope of enzymology has expanded rapidly over the last century, from an early focus on the chemical and catalytic mechanisms of individual enzymes to more recent efforts to understand enzyme action in the context of dynamic, functional biological systems consisting of many interacting enzymes and proteins. Continuing progress in probing the link between molecular structure and function now promises to pave the way for a deeper understanding of the evolution and behavior of the complex biological systems that govern cellular behavior.
Annotations of enzyme function provide critical starting points for generating and testing biological hypotheses, but the quality of functional annotations is hindered by uncertain assignments for uncharacterized sequences and by the relative sparseness of validated experimental data. Given the relentless increase in genomic data, new thinking and validation methods are urgently needed to provide high confidence in enzyme functional assignments.
Protein improvement strategies today involve widely varying combinations of rational design with random mutagenesis and screening. To make further progress—defined as making subsequent protein engineering problems easier to solve—protein engineers must critically compare these strategies and eliminate less effective ones.
The 2009 ESBOC meeting covered advances in synthesis, biosynthesis and biological mechanisms of vitamins and cofactors. Recent exciting developments in the field include the development of 'green' chemistry for manufacture of vitamins, the discovery that some vitamins act directly to regulate gene expression via riboswitches, and initial attempts to exploit the potential of vitamin analogs as therapeutic drugs.
The parallel determination of more than 100 absolute intracellular metabolite concentrations by isotope-labeled HPLC-MS allowed a comprehensive analysis of the cellular state, its metabolic capacities and modes of regulation. Among other findings, it became obvious that for most enzymes the concentrations were above the Km values, which indicates a trend toward saturation of most enzyme active sites.
Random mutations usually destabilize protein tertiary structure. Overexpression of the chaperonin GroEL/GroES protects evolving proteins from the destabilizing effects of adaptive mutations and improves the quantity and quality of enzyme variants with modified function.
Insights gained from advanced techniques and large datasets are charting new courses in enzymological research. In this issue, we feature a collection of articles highlighting the current ideas and future challenges that are redirecting research in the field.