The chemoton story
Eörs Szathmáry
Collegium Budapest
Eötvös University Budapest
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)
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!
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
The investigation of life criteria:
absolute criteria
1.
2.
3.
4.
5.
Inherent unity
Metabolism
Inherent stability
Information carrying subsystem
Processes regulated and controlled by a
programme
VERBAL AND PHENOMENOLOGICAL
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
The eukaryotic cell is very
complex—too complex!
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
Gánti’s chemoton model
metabolism
template
copying
membrane
growth
ALL THREE SUBSYSTEMS ARE AUTOCATALYTIC
Organisation of chemical systems
into a supersystem (1974)
• CHEMOTON: a particular supersystem which is
also a biological minimal system
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
Enzymes and cycle stoichiometry
Very
important:
the cyclic
process sign
with the
number of
turns
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
A self-reproducing vesicle (1978)
• Metabolism and reproduction
• No genetic subsystem
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
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
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
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
Structures form in 3 dimensions...
• …and are suggestive of enzymatic capability
Some RNA molecules act as
enzymes (ribozymes) today
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
The assembly of RNA structures
• Combinatorial
assembly of RNA
structures
• Submitted to selection
for function between
chemotons
• 1979
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
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
The energetic logic of catalysis
Without catalysis
The formose ‘reaction’
formaldehyd
e
autocatalysi
s
glycolaldehyde
Butlerow, 1861
Is this just logical or also
historical order?
• How much evolution did take place (presumably
on surfaces) before protocells appeared?
Classification of replicators
Limited
heredity
Holistic
formose
Modular
Von
Kiedrowski
Unlimited
heredity
genes
Limited
(# of individuals)  (# of types)
Unlimited
(# of individuals) << (# of types)
Units of evolution and units of life
viruses
memes
Units of evolution
bacteria,
protists,
etc.
mules
sterilized
workers
nondividing
cells
Units of life
Pathways of supersystem evolution
metabolism
MB
boundary
MT
template
BT
MBT
Further reading
• The OUP book
• Forthcoming:
CHEMOTON
THEORY I and II,
Kluwer, 2004