Eduard Buchner, working in Tübingen in 1897, was grinding yeast cells under high pressure to extract a clean protein fraction, and added a concentrated sugar solution as a preservative. The sugar started fermenting. The cell-free yeast juice, with no living cells anywhere in it, was producing carbon dioxide and ethanol exactly as if the cells had still been alive. Fermentation — which Louis Pasteur had argued required a living organism, the central textual battleground of nineteenth-century vitalism — turned out to be chemistry. The agent was a substance, not a life force. Buchner called it zymase, won the 1907 Nobel Prize in Chemistry, and reset the foundations of biology in one paper. The proteins that perform such catalysis are what we now call enzymes.
An enzyme is a protein (occasionally an RNA) that catalyses a specific chemical reaction by lowering its activation energy without itself being consumed. The rate enhancements are enormous. Carbonic anhydrase accelerates its reaction by a factor of ~10⁷. OMP decarboxylase manages ~10¹⁷, the largest rate enhancement known, turning a reaction that would take 78 million years uncatalysed into one that completes in 18 milliseconds. Without enzymes the chemistry of life would take longer than the universe has existed. Linus Pauling's 1948 transition-state stabilization theory gave the unifying explanation: an enzyme binds the transition state more tightly than substrate or product, lowering the activation energy by the difference in binding free energies. The kinetic framework arrived earlier. Leonor Michaelis and Maud Menten, in Berlin in 1913, derived v = V_max · [S] / (K_m + [S]); the fastest enzymes operate as quickly as molecules can find each other in solution. Emil Fischer's 1894 lock-and-key metaphor captured specificity but missed dynamics; Daniel Koshland's 1958 induced-fit model corrected it. The catalytic strategies fall into a small set — general acid-base catalysis, covalent catalysis, metal-ion catalysis (zinc in carbonic anhydrase, magnesium in DNA polymerase), electrostatic preorganization (Arieh Warshel's 2013 Nobel work) — and most enzymes combine several. Thomas Cech (1982) and Sidney Altman (1983) discovered RNA enzymes — ribozymes — proving nucleic acids could catalyse reactions too; the shared 1989 Nobel was major evidence for an RNA world preceding contemporary life. The ribosome itself, the protein-making machine in every cell, is at its catalytic core a ribozyme.
Enzymes are the largest single class of drug targets: roughly half of all FDA-approved small-molecule drugs are enzyme inhibitors. Statins block HMG-CoA reductase in cholesterol biosynthesis; aspirin irreversibly acetylates cyclooxygenase; imatinib (Gleevec) inhibits the BCR-ABL tyrosine kinase that drives chronic myeloid leukemia, the prototype targeted-cancer therapy whose successors — more than 80 tyrosine-kinase inhibitors in clinical use — are mostly designed by active-site modelling. β-lactam antibiotics inhibit bacterial transpeptidases; nirmatrelvir (Paxlovid, 2021) targets a SARS-CoV-2 protease. Enzyme engineering by directed evolution (Frances Arnold, 2018 Nobel) has produced industrial enzymes for biofuels. The RFdiffusion / ProteinMPNN generative models from the David Baker lab (2024 Chemistry Nobel) now design novel enzymes from scratch with measurable activity for reactions evolution never produced.