The chemoton story

1. The chemoton story Eörs Szathmáry Collegium Budapest Eötvös University Budapest

2. Tibor Gánti • Born in 1933 • A chemical engineer • Patents in industrial biochemistry • Syntheses using the controlled operation of enzymatic reaction networks • First book on molecular biology in Hungary (1966)

3. The first edition of the Principles • A serious book in a popular science disguise • There was no other way to publish • Proposal included the term “chemoton” • ‘reductionist’ and ‘vitalist’ at the same time!

4. The latest edition: OUP 2003 • After several editions in Hungarian • Two previous books (the Principles and Contra Crick) plus one essay • Essays appreciating the biological and philosophical importance

5. The investigation of life criteria: absolute criteria • Inherent unity • Metabolism • Inherent stability • Information carrying subsystem • Processes regulated and controlled by a programme VERBAL AND PHENOMENOLOGICAL

6. Quest for a biological minimal system • Chemical supersystem • Should be conceptually as simple as possible • Must not necessarily be realizable in its simplest form • Comparison with other elementary units (such as the elementary cell in crystallography) • FORMAL AND EXACT

7. The eukaryotic cell is very complex—too complex!

8. The simplest cells are bacterial • THUS we want to explain the origin of some primitive bacterium-like cell • Even present-day bacteria are far too complex • The main problem is the genetic code

9. Gánti’s chemoton model metabolism template copying membrane growth ALL THREE SUBSYSTEMS ARE AUTOCATALYTIC

10. Organisation of chemical systems into a supersystem (1974) • CHEMOTON: a particular supersystem which is also a biological minimal system

11. Chemical cycles are metabolic engines (1971) • The cycle as a whole is a catalyst • The Noble prize of Szent-Györgyi was awarded for catalysis by fumaric acid • Krebs has recognized the whole cycle • Enzymes are superimposed on the metabolic cycle

12. Enzymes and cycle stoichiometry Very important: the cyclic process sign with the number of turns

13. At the heart of the chemoton… • …there is a metabolic cycle • It is autocatalytic • Produces the raw materials for the functioning of all subsystems at the expense of the difference between nutrients and waste • Has homeostatic capacity • The Calvin cycle and the reductive citric acid cycle are such core systems (controlled by enzymes) today

14. A self-reproducing vesicle (1978) • Metabolism and reproduction • No genetic subsystem

15. The informational subsystem • The pVn molecule consists of n molecules of V • Result of template polycondensation • R is the by-product, necessary for the formation of the membranogenic molecule T • Information carried by quantity, frequency (composition), or sequence of signs • Importance of sequence increases in evolution

16. The fission of the chemoton • Membrane surface doubled • Quantity of internal materials doubled • Assume spherical shape • Concentration cannot be kept with a growing sphere: volume increases with the cubic of the radius • Volume of sphere with a surface are doubled would be more than doubled

17. Chemoton fission II • More detailed calculations based on continuum mechanics • Continuous distortion of the spherical shape • Final resolution: two new spheres with size identical to that of the parental sphere • STRICT STOICHIOMETRIC COUPLING BETWEEN THE GROWTH OF THE SUBSYSTEMS

18. Most biological reactions are catalyzed by protein enzymes Without catalysis the reaction is slow S  P The catalyzed reaction is fast S + E  ES ES  EP EP  E + P

19. Structures form in 3 dimensions... • …and are suggestive of enzymatic capability

20. Some RNA molecules act as enzymes (ribozymes) today

21. Test-tube selection experiments yield novel ribozymes and show that • Catalysis of C-C bonds was feasible • Even hydrophobic molecules can be specifically recognized • The RNA world is likely to have been metabolically complex

22. The assembly of RNA structures • Combinatorial assembly of RNA structures • Submitted to selection for function between chemotons • 1979

23. The channelled assembly of ribozymes (1983) • The presence of substrates gives guidance to ribozyme assembly • Good enzymes and bad enzymes will affect the fitness of the chemotons

24. The major open issue • Is the chemoton viable without some form of enzymatic catalysis? • Does membrane confinement provide enough metabolite channelling? • Is non-enzymatic replication feasible at all? • EVEN IF THE CHEMOTON IS NOT FEASIBLE WITHOUT ENZYMES, IT REMAINS THE ABSTRACTION OF THE ESSENTIAL SYSTEM THAT THE ENZYMES REGULATE

25. The energetic logic of catalysis Without catalysis

26. The formose ‘reaction’ formaldehyde autocatalysis glycolaldehyde Butlerow, 1861

27. Is this just logical or also historical order? • How much evolution did take place (presumably on surfaces) before protocells appeared?

28. Classification of replicators Limited (# of individuals)  (# of types) Unlimited (# of individuals) << (# of types)

29. Units of evolution Units of life Units of evolution and units of life mules sterilized workers nondividing cells bacteria, protists, etc. viruses memes

30. Pathways of supersystem evolution metabolism MB boundary MT MBT template BT

31. Further reading • The OUP book • Forthcoming: CHEMOTON THEORY I and II, Kluwer, 2004