Table 1.
The history of cell-free fundamental research and in vitro biomanufacturing accompanied with milestones.
| Year | Leaders | Milestone (Award) | References |
|---|---|---|---|
| Milestones for cell-free fundamental research | |||
| 1907 | Arthur Harden, Hans Karl August Simon von Euler-Chelpin | Fermentation of sugar and fermentative enzymes (Nobel Chemistry 1929) | [109] |
| 1930s | James Batcheller Sumner, John Howard Northrop, Wendell Meredith Stanley | Preparation of enzymes and virus proteins in a pure form (Nobel Chemistry 1946) | [[110], [111], [112]] |
| 1940s | Hans Krebs | Discovery of the citric acid cycle (Nobel Physiology 1953) | [113] |
| 1940s | Melvin Calvin | Carbon dioxide assimilation in plants (Nobel Chemistry 1961) | [114] |
| 1960s | Francois Jacob, Jacques Monod, Andre Lwoff | Discoveries concerning genetic control of enzyme and virus synthesis (Nobel Physiology or Medicine 1965) | [115] |
| 1960s | Robert William Holley, Har Gobind Khorana, Marshall Warren Nirenbrg | Interpretation of the genetic code and its function in protein synthesis (Nobel Physiology or Medicine 1968) | [116,117] |
| 1970s | Werner Arber, Daniel Nathans, Hamilton Othanel Smith | Discovery of restriction enzymes and their application to problems of molecular genetics (Nobel Physiology or Medicine 1978) | [[118], [119], [120]] |
| 1990s | Kary Banks Mullis, Michael Smith | Invention of the polymerase chain reaction (PCR) method; Establishment of site-directed mutagenesis with application to protein studies (Nobel Chemistry 1993) | [121,122] |
| 2000s- | Natural/non-natural product synthesis used as pharmaceuticals, biochemicals and biofules (e.g., CFPS) | [24,35] | |
| Milestones for in vitro biomanufacturing | |||
| 1897 | Eduard Buchner | Cell-free ethanol fermentation by nonliving yeast lysate (Nobel Chemistry 1907) | [123] |
| 1960s-1970s | One-enzyme biotransformation for high fructose corn syrup production (i.e., more than 20 million tonnes yearly) and semi-synthetic antibiotics (e.g., cephalosporin) | [37] | |
| 1990s | Multi-enzyme biotransformation for fine chemicals and pharmaceuticals production | [36,40,41] | |
| 1990s | Cell-free protein synthesis | [35] | |
| 2000s | Hydrogen, artificial starch, and inositol production | [15,32,92] | |