“ I have never met a dull enzyme ”
15/12/2015 | Comments Off on “ I have never met a dull enzyme ”
Dr. Arthur Kornberg, biochemist and Nobel prize recipient who devoted his professional life to the study of enzymes, is often quoted for his statement that he never met a dull enzyme. In his biographical essay (1), Arthur describes his professional career and scientific research and how he fell in love with enzymes and remained faithful to them ever since.
Entering medical school in 1937, when the importance of enzymes had still not entered the textbooks, Arthur felt that Biochemistry was a rather dull course. In 1942, he joined the Nutrition Laboratory at the National Institute of Health and the ongoing work on the discovery of vitamins and their importance for human nutrition. The exact roles of vitamins in the body was at the time unclear but became elucidated through the study of enzymes in the next few decades. Looking for a new scientific frontier and fascinated by the new “one gene-one enzyme” hypothesis, Arthur joined the enzyme hunters. Now, biochemistry was starting to be interesting.
After setting up his own lab at NIH in 1948, Arthur started working on an enzyme he called nucleotide pyrophosphatase which he could readily extract from potatoes in free soluble form and which led to the discovery of the mechanism of nucleotidyl transfer from a nucleoside triphosphate and the biosynthesis of coenzymes. And as Arthur states in his essay: “What a wondrous enzyme, the humble potato pyrophosphatase! It helped solve an aspect of NADP structure, set up the discovery of coenzyme biosynthesis, and with it a major theme in biochemistry, and then led me on to the enzymes that assemble DNA, genes, and chromosomes.”
During the 1950s, a decade that also gave us the historic discovery by Watson and Crick of the structure of the DNA double helix, Arthur followed his fascination with enzymes and the work on pyrophosphatase and single nucleotides to search for enzymes important for the assembly of many nucleotides into chains of nucleic acids (RNA and DNA). By then, the bacterial species Escherichia coli had become the favoured organism for genetic and biochemical studies as well as a source for enzymes. After turning their efforts to look for enzymes of DNA synthesis, the progress by Kornberg and his colleagues was relatively rapid and led to the discovery of an enzyme in Escherichia coli which they would name DNA polymerase. The later discovery and isolation by other scientists of a thermostable DNA polymerase from the hot spring bacteria Thermus aquaticus (Taq DNA polymerase – see figure) became the basis for the Polymerase Chain Reaction, a technique for in vitro amplification of DNA used today in laboratories around the world.
The subsequent discovery of DNA ligase in 1967 made it possible to replicate DNA from a bacteriophage with DNA polymerase and then seal the product using the DNA ligase to eventually produce a synthetic DNA that could infect E.coli and demonstrate biological activity equal to the original bacteriophage DNA. Catching the attention of the media at the time, it seemed like life had been created in a test tube. Disregarding the overstatements by the press (e.g. “Creation of Life Rates Best of Science Stories in 1967”), it became clear that the road was now open to the manipulation of genes and creation of novel DNA.
Dr. Arthur Kornberg continued his research on the enzymology of DNA replication for decades to come. The advancement in the field saw the discovery of numerous enzymes being active on nucleic acids including enzymes being able to manipulate DNA in various ways including DNA polymerases with different properties, single-strand and double-strand DNA ligases, polynuclotide kinases, DNA helicases, single-strand binding proteins and large spectrum of restriction enzymes being able to cut DNA at specific positions determined by the DNA sequence. The ability to manipulate DNA in such specific and precise ways ensured that these enzymes became important tools in the tool chests of molecular biologists and geneticists and paved the way to the biotechnological revolution we witness today.
Dr Arthur Kornberg received the Nobel Prize in Physiology or Medicine in 1959 for his discovery of “the mechanism in the biological synthesis of deoxyribonucleic acid (DNA)”. He died on October 26, 2007 at the age of 89 (2)