News and Publications
The Skaggs Institute For Chemical Biology
Scientific Report 1997-1998
Self-Organized Autocatalytic Networks
M.R. Ghadiri, D.T.Y. Bong, K. Broo, A.J. Kennan, K. Kumar, A. Saghatelian,
Understanding the molecular basis of life has been the central goal of chemical
and biological sciences. However, little is known about the fundamental properties
that distinguish the chemistry of living systems, which gives rise to animate
characteristics, from inanimate in vitro chemical transformations. Recent advances
in the mathematical understanding of complex nonlinear systems, chemistry, molecular
biology, and analytical sciences are allowing a new, broad, and unique attack
on the fundamental understanding of living processes.
The approach that we use is based on the following premises. Living systems
are considered autonomous self-reproducing entities that operate on the basis
of information. Information is originated at the molecular level by covalent
chemistry, transferred and processed through noncovalent chemistry, expanded
in complexity at the system level, and ultimately changed through reproduction
and natural selection. In a living system, the complex blend of nonlinear molecular
information-transfer processes is thought to bring about a coherent self-organized
chemical system--a collective of interacting and interdependent molecular species,
a "molecular ecosystem"--that as a whole can have emergent properties far greater
than the simple sum of its chemical constituents. Therefore, to understand and
ultimately mimic the properties of living systems, we are defining the basic
forms of self-organized autocatalytic chemical networks, how the networks can
be constructed, and how the interplay of information and nonlinear catalysis
can lead to the expression of emergent properties (Fig. 1).
The basic methods required for the study of self-organized networks were
resolved through rational de novo design of catalysts that form amide bonds (ligases
and replicases) for sequence-specific peptide-fragment condensation reactions.
These catalysts in turn have enabled the design and study of simple self-organized
reciprocal, autocratic, and mutualistic networks that begin to display some of
the basic properties often associated with living systems, such as selection,
symbiosis, and error correction. Our current efforts focus on the design and
characterization of more complex networks and molecular ecosystems.
Lee, D.H., Severin, K., Ghadiri, M.R. Autocatalytic networks: The
transition from molecular self-replication to ecosystems. Curr. Opin. Chem. Biol.
Lee, D.H., Severin, K., Yokobayashi, Y., Ghadiri, M.R. Emergence of
symbiosis in peptide self-replication through a hypercyclic network. Nature 390:591,
Severin, K., Lee, D.H., Martinez, J.A., Vieth, M., Ghadiri, M.R. Dynamic
error-correction in autocatalytic peptide networks. Angew. Chem. Int. Ed. 37:126,