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Biochemistry & Enzymatic Catalysis: Major Case Studies & Paradigm Shifts

Encyclopedia/1. The Cosmos & The Natural World/2. Physics & Chemistry/03. Chemistry & Periodic Table of Elements  •  Curated by Admin Timeline.sg

This timeline traces the evolution of biochemistry and enzymatic catalysis from the early discovery of enzymes to modern breakthroughs like CRISPR and directed evolution, highlighting key experimental findings and paradigm shifts that shaped our understanding of biological catalysts.

Chronological Storyline (40 Milestones)

1833 CE

Discovery of Diastase, the First Enzyme

Anselme Payen and Jean-François Persoz isolate diastase from malt, the first known enzyme, demonstrating that a chemical substance can catalyze the breakdown of starch. This marks the birth of enzymology. #biochemistry #history

1856 CE

Pasteur's Fermentation Experiments

Louis Pasteur demonstrates that fermentation is caused by living microorganisms, laying the foundation for understanding biological catalysis and later linking enzymes to cellular processes. #biochemistry #microbiology

Pasteur's Fermentation Experiments
Pasteur's Fermentation Experiments
By Paul Nadar - File:Louis Pasteur, foto av Paul Nadar.jpg, Public domain, https://commons.wikimedia.org/w/index.php?curid=28039885
1897 CE

Buchner's Cell-Free Fermentation

Eduard Buchner shows that yeast extract can ferment sugar without living cells, proving that enzymes are responsible for fermentation and earning the Nobel Prize in Chemistry in 1907. #biochemistry #enzymes

Buchner's Cell-Free Fermentation
Buchner's Cell-Free Fermentation
By Unknown author - http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner.html, Public domain, https://commons.wikimedia.org/w/index.php?curid=18253176
1913 CE

Michaelis-Menten Kinetics

Leonor Michaelis and Maud Menten publish their model of enzyme kinetics, introducing the Michaelis constant (Km) and revolutionizing the quantitative study of enzyme catalysis. #biochemistry #kinetics

Michaelis-Menten Kinetics
Michaelis-Menten Kinetics
By Athel cb - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=130422583
1926 CE

Sumner Crystallizes Urease

James B. Sumner crystallizes urease, providing the first direct evidence that enzymes are proteins (Nobel Prize in Chemistry, 1946). This landmark experiment settles the debate about the chemical nature of enzymes. #biochemistry #enzymes

Sumner Crystallizes Urease
Sumner Crystallizes Urease
By Unknown author - http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1946/sumner.html, Public domain, https://commons.wikimedia.org/w/index.php?curid=18260359
1930 CE

Northrop and Stanley Crystallize Pepsin and Trypsin

John H. Northrop and Wendell M. Stanley crystallize pepsin and trypsin, further confirming the protein nature of enzymes and earning the Nobel Prize in Chemistry in 1946 alongside Sumner. #biochemistry #enzymes

Northrop and Stanley Crystallize Pepsin and Trypsin
Northrop and Stanley Crystallize Pepsin and Trypsin
By Unknown author - http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1946/northrop.html, Public domain, https://commons.wikimedia.org/w/index.php?curid=18260391
1937 CE

Krebs Cycle Elucidated

Hans Krebs describes the citric acid cycle (Krebs cycle), the central metabolic pathway for aerobic respiration, a paradigm shift in understanding cellular energy metabolism. #biochemistry #metabolism

Krebs Cycle Elucidated
Krebs Cycle Elucidated
By Narayanese, WikiUserPedia, YassineMrabet, TotoBaggins - http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=TCA. Image adapted from Image:Citric acid cycle noi.svg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6217701
1941 CE

Discovery of Coenzyme A

Fritz Lipmann discovers coenzyme A (CoA), a crucial cofactor in acyl group transfer reactions, and receives the Nobel Prize in Physiology or Medicine in 1953. #biochemistry #coenzymes

Discovery of Coenzyme A
Discovery of Coenzyme A
By NEUROtiker - Own work, Public domain, https://commons.wikimedia.org/w/index.php?curid=1555660
1951 CE

Pauling Proposes Alpha-Helix Structure

Linus Pauling publishes the alpha-helix and beta-sheet models of protein secondary structure, based on X-ray crystallography and theoretical reasoning, revolutionizing structural biology. #biochemistry #structuralbiology

Pauling Proposes Alpha-Helix Structure
Pauling Proposes Alpha-Helix Structure
By Theislikerice - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=81729199
1951 CE

Sanger Sequences Insulin

Frederick Sanger determines the complete amino acid sequence of bovine insulin, providing the first primary structure of a protein and winning the Nobel Prize in Chemistry in 1958. #biochemistry #proteomics

Sanger Sequences Insulin
Sanger Sequences Insulin
By User:AtikaAtikawa - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=107840330
1953 CE

Watson and Crick Discover DNA Structure

James Watson and Francis Crick propose the double helix structure of DNA, a foundational event for molecular biology and biochemistry, explaining genetic replication and information storage. #biochemistry #genetics

Watson and Crick Discover DNA Structure
Watson and Crick Discover DNA Structure
By 84user adapting file originally uploaded by Richard Wheeler (Zephyris) at en.wikipedia - Derived from File:DNA orbit animated.gif originally from here., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6285050
1956 CE

Anfinsen's Dogma of Protein Folding

Christian Anfinsen demonstrates that ribonuclease can refold spontaneously in vitro, leading to the thermodynamic hypothesis that the native structure is determined by the amino acid sequence (Nobel Prize in Chemistry, 1972). #biochemistry #proteinfolding

Anfinsen's Dogma of Protein Folding
Anfinsen's Dogma of Protein Folding
By Dcrjsr - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=18719297
1957 CE

Jacob and Monod Propose the Operon Model

François Jacob and Jacques Monod introduce the operon concept to explain gene regulation in bacteria, highlighting the role of repressor proteins and allostery (Nobel Prize in Physiology or Medicine, 1965). #biochemistry #generegulation

1960 CE

Reversible Protein Phosphorylation Discovered

Edmond Fischer and Edwin Krebs discover that reversible phosphorylation of proteins regulates enzyme activity, a paradigm-shifting finding in signal transduction (Nobel Prize in Physiology or Medicine, 1992). #biochemistry #signaling

Reversible Protein Phosphorylation Discovered
Reversible Protein Phosphorylation Discovered
By Thomas Splettstoesser - from PDB is 1T29, rendered with open source program PyMol (www.pymol.org), CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=1348311
1961 CE

Allosteric Regulation Articulated

Jacques Monod, Jean-Pierre Changeux, and François Jacob formalize the theory of allosteric regulation, explaining how enzymatic activity can be modulated by effectors binding at sites distinct from the active site. #biochemistry #enzymes

Allosteric Regulation Articulated
Allosteric Regulation Articulated
By Tenthkrige (talk). Tenthkrige - Own work (Original text: I (Tenthkrige (talk)) created this work entirely by myself.), CC0, https://commons.wikimedia.org/w/index.php?curid=85816837
1965 CE

First Chemical Synthesis of Insulin (China)

A team of Chinese scientists at Nankai University successfully synthesizes bovine insulin, the first complete synthesis of a protein, demonstrating the power of organic chemistry in biochemistry. #biochemistry #synthesis

1969 CE

Solid-Phase Peptide Synthesis Developed

Bruce Merrifield invents solid-phase peptide synthesis, enabling automated production of peptides and small proteins (Nobel Prize in Chemistry, 1984). This technique accelerates biochemical research and drug development. #biochemistry #synthesis

Solid-Phase Peptide Synthesis Developed
Solid-Phase Peptide Synthesis Developed
By Algertzars (talk) - Own work, Public domain, https://commons.wikimedia.org/w/index.php?curid=65305772
1970 CE

Restriction Enzymes Discovered

Werner Arber, Daniel Nathans, and Hamilton Smith discover restriction endonucleases, which cut DNA at specific sequences, enabling recombinant DNA technology (Nobel Prize in Physiology or Medicine, 1978). #biochemistry #genetics

1972 CE

Anfinsen Wins Nobel for Protein Folding

Christian Anfinsen receives the Nobel Prize in Chemistry for his work on ribonuclease folding, establishing that the amino acid sequence dictates three-dimensional structure (the thermodynamic hypothesis). #biochemistry #proteinfolding

Anfinsen Wins Nobel for Protein Folding
Anfinsen Wins Nobel for Protein Folding
By Hubbard, Edward A.; National Institutes of Health - http://profiles.nlm.nih.gov/KK/B/B/B/G/, Public domain, https://commons.wikimedia.org/w/index.php?curid=2949195
1975 CE

Hybridoma Technology for Monoclonal Antibodies

Georges Köhler and César Milstein develop hybridoma technology to produce monoclonal antibodies, revolutionizing immunology and diagnostics (Nobel Prize in Physiology or Medicine, 1984). #biochemistry #immunology

Hybridoma Technology for Monoclonal Antibodies
Hybridoma Technology for Monoclonal Antibodies
By Adenosine - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9659630
1981 CE

Catalytic RNA (Ribozymes) Discovered

Thomas Cech and Sidney Altman independently discover that RNA can catalyze chemical reactions, challenging the dogma that all enzymes are proteins (Nobel Prize in Chemistry, 1989). #biochemistry #rna

Catalytic RNA (Ribozymes) Discovered
Catalytic RNA (Ribozymes) Discovered
By William G. Scott - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2257831
1985 CE

Polymerase Chain Reaction (PCR) Invented

Kary Mullis develops the polymerase chain reaction (PCR), a rapid method to amplify DNA segments, transforming molecular biology and diagnostics (Nobel Prize in Chemistry, 1993). #biochemistry #molecularbiology

Polymerase Chain Reaction (PCR) Invented
Polymerase Chain Reaction (PCR) Invented
By Madprime - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=2104468
1987 CE

Directed Evolution of Enzymes

Frances Arnold pioneers directed evolution, a method to engineer enzymes with improved or novel functions through iterative mutation and selection, ushering in a new era of protein engineering (Nobel Prize in Chemistry, 2018). #biochemistry #proteinengineering

Directed Evolution of Enzymes
Directed Evolution of Enzymes
By Thomas Shafee - Thomas, Shafee, (2014). "Evolvability of a viral protease: experimental evolution of catalysis, robustness and specificity". PhD Thesis. University of Cambridge., CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=37193303
1990 CE

Structure of Bacteriorhodopsin Resolved

Richard Henderson and Nigel Unwin use electron crystallography to determine the structure of bacteriorhodopsin at 3.5 Å, a milestone in membrane protein structural biology. #biochemistry #structuralbiology

Structure of Bacteriorhodopsin Resolved
Structure of Bacteriorhodopsin Resolved
By Deposition authors: Weinert, T., Skopintsev, P., James, D., Kekilli, D., Furrer, A., Bruenle, S., Mous, S., Nogly, P., Standfuss, J.; Visualization author: Synpath - Atom coordinates: https://www.rcsb.org/structure/6RQP; Visualization: Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=132775070
1992 CE

Structure of Protein Kinase A Solved

Susan Taylor and colleagues determine the three-dimensional structure of protein kinase A, providing the first atomic view of a protein kinase and insights into phosphorylation regulation. #biochemistry #signaling

Structure of Protein Kinase A Solved
Structure of Protein Kinase A Solved
By Deposition authors: Zheng, J., Knighton, D.R., Xuong, N.-H., Taylor, S.S., Sowadski, J.M., Ten Eyck, L.F.; visualization author: User:Astrojan - https://www.rcsb.org/structure/1cmk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=111774827
1994 CE

Green Fluorescent Protein (GFP) Cloned

Martin Chalfie clones the gene for green fluorescent protein (GFP) from the jellyfish Aequorea victoria, enabling its use as a fluorescent marker in live cells (Nobel Prize in Chemistry, 2008). #biochemistry #imaging

Green Fluorescent Protein (GFP) Cloned
Green Fluorescent Protein (GFP) Cloned
By Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute - https://www.ebi.ac.uk/pdbe/static/entry/1ema_deposited_chain_front_image-800x800.png, displayed on https://www.ebi.ac.uk/pdbe/entry/pdb/1ema, Public domain, https://commons.wikimedia.org/w/index.php?curid=6307286
1995 CE

First Complete Bacterial Genome Sequenced

The genome of Haemophilus influenzae is the first to be fully sequenced, marking the beginning of genomics and enabling systems-level biochemistry. #biochemistry #genomics

First Complete Bacterial Genome Sequenced
First Complete Bacterial Genome Sequenced
By Stefan Walkowski - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=41492226
1998 CE

RNA Interference Discovered

Andrew Fire and Craig Mello discover RNA interference (RNAi), a gene-silencing mechanism mediated by double-stranded RNA (Nobel Prize in Physiology or Medicine, 2006). #biochemistry #generegulation

RNA Interference Discovered
RNA Interference Discovered
By Dan Cojocari ✉·✍· - Own, This W3C-unspecified vector image was created with Adobe Illustrator., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8697221
2001 CE

Imatinib Approved as Targeted Cancer Therapy

Imatinib (Gleevec), a tyrosine kinase inhibitor targeting Bcr-Abl, receives FDA approval, demonstrating the power of rational drug design based on biochemical knowledge. #biochemistry #pharmacology

Imatinib Approved as Targeted Cancer Therapy
Imatinib Approved as Targeted Cancer Therapy
By Fuse809 - Own work, Public domain, https://commons.wikimedia.org/w/index.php?curid=30346575
2003 CE

Human Genome Project Completed

The Human Genome Project publishes the complete sequence of the human genome, providing a blueprint for biomedical research and catalyzing advances in genomics biochemistry. #biochemistry #genomics

Human Genome Project Completed
Human Genome Project Completed
By U.S. Department of Energy, Human Genome Project - http://www.ornl.gov/hgmis, Public domain, https://commons.wikimedia.org/w/index.php?curid=2485616
2005 CE

SHAPE Method for RNA Structure Probing

The SHAPE (Selective 2'-Hydroxyl Acylation Analyzed by Primer Extension) method is developed to probe RNA secondary structure at nucleotide resolution, advancing RNA biochemistry. #biochemistry #rna )

2006 CE

Induced Pluripotent Stem Cells (iPS Cells)

Shinya Yamanaka discovers that differentiated cells can be reprogrammed into pluripotent stem cells by expressing specific transcription factors, opening new avenues in regenerative medicine (Nobel Prize 2012). #biochemistry #stemcells

Induced Pluripotent Stem Cells (iPS Cells)
Induced Pluripotent Stem Cells (iPS Cells)
By NIH Image Gallery from Bethesda, Maryland, USA - Human induced pluripotent stem cell colony, Public domain, https://commons.wikimedia.org/w/index.php?curid=114900547
2008 CE

Next-Generation Sequencing Revolution

Next-generation sequencing (NGS) technologies emerge, enabling rapid, low-cost genome sequencing and transforming systems biochemistry, personalized medicine, and metagenomics. #biochemistry #genomics

2012 CE

CRISPR-Cas9 Genome Editing

Emmanuelle Charpentier and Jennifer Doudna repurpose the CRISPR-Cas9 bacterial immune system for programmable genome editing, a revolutionary tool for biochemistry and genetics (Nobel Prize in Chemistry, 2020). #biochemistry #genetics

CRISPR-Cas9 Genome Editing
CRISPR-Cas9 Genome Editing
By Boghog - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=68597347
2013 CE

Cryo-Electron Microscopy Achieves Atomic Resolution

Advances in cryo-EM enable near-atomic resolution for macromolecular structures, a breakthrough that wins the Nobel Prize in Chemistry in 2017 (Jacques Dubochet, Joachim Frank, Richard Henderson). #biochemistry #structuralbiology

Cryo-Electron Microscopy Achieves Atomic Resolution
Cryo-Electron Microscopy Achieves Atomic Resolution
By Hiramano92 - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=121225443
2015 CE

Nobel for DNA Repair Mechanisms

Tomas Lindahl, Paul Modrich, and Aziz Sancar receive the Nobel Prize in Chemistry for mapping how cells repair damaged DNA, elucidating fundamental biochemical pathways. #biochemistry #dna

Nobel for DNA Repair Mechanisms
Nobel for DNA Repair Mechanisms
By Unknown author, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=449797
2016 CE

Directed Evolution of Enzymes Wins Nobel

Frances Arnold is awarded the Nobel Prize in Chemistry for directed evolution of enzymes, along with George Smith and Gregory Winter for phage display, revolutionizing protein engineering. #biochemistry #proteinengineering

2018 CE

First Crystal Structure of Ribosome Solved

Venkatraman Ramakrishnan, Thomas Steitz, and Ada Yonath win the Nobel Prize in Chemistry for determining the structure of the ribosome, the protein synthesis machinery. #biochemistry #structuralbiology

First Crystal Structure of Ribosome Solved
First Crystal Structure of Ribosome Solved
By Vossman - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6865434
2020 CE

mRNA Vaccines for COVID-19

The rapid development of mRNA vaccines (Pfizer/BioNTech and Moderna) against SARS-CoV-2 relies on lipid nanoparticle delivery of modified mRNA, a triumph of biochemistry and nanotechnology. #biochemistry #vaccines

mRNA Vaccines for COVID-19
mRNA Vaccines for COVID-19
By Shuqin Xu, Kunpeng Yang, Rose Li, and Lu Zhang - Xu, S.; Yang, K.; Li, R.; Zhang, L. mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection. Int. J. Mol. Sci. 2020, 21, 6582. https://doi.org/10.3390/ijms21186582, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=106937729
2021 CE

AlphaFold Predicts Protein Structures

DeepMind's AlphaFold2 achieves remarkable accuracy in predicting protein three-dimensional structures from amino acid sequences, revolutionizing structural biochemistry and drug discovery. #biochemistry #AI

AlphaFold Predicts Protein Structures
AlphaFold Predicts Protein Structures
By Kathryn Tunyasuvunakool, Jonas Adler, Zachary Wu, Tim Green, Michal Zielinski, Augustin Žídek, Alex Bridgland, Andrew Cowie, Clemens Meyer, Agata Laydon, Sameer Velanka *, Gerard J Kleywegt *, Alex Bateman *, Richard Evans, Alexander Pritzel, Michael Figurnov, Olaf Ronneberger, Russ Bates, Simon A. A. Kohl, Anna Potapenko, Andrew J Ballard, Bernardino Romera-Paredes, Stanislav Nikolov, Rishub Jain, Ellen Clancy, David Reiman, Stig Petersen, Andrew Senior, Koray Kavukcuoglu, Ewan Birney *, Pushmeet Kohli, John Jumper, Demis Hassabis - https://deepmind.google/blog/enabling-high-accuracy-protein-structure-prediction-at-the-proteome-scale/, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=188769148