Evolution metabolic pathways

A self-replicating polymer would quickly use up available supplies of precursors provided by the relatively slow processes of prebiotic chemistry. Thus, from an early stage in evolution, metabolic pathways would be required to generate precursors efficiently, with the synthesis of precursors presumably catalyzed by ri-bozymes. The extant ribozymes found in nature have a limited repertoire of catalytic functions, and of the ribozymes that may once have existed, no trace is left. To explore the RNA world hypothesis more deeply, we need to know whether RNA has the potential to catalyze the many different reactions needed in a primitive system of metabolic pathways. 

Algal blooms in fresh water ponds occasionally poison livestock and waterfowl. Axenic cultures of Anabaena flos-aquae NRC 44-1 were shown to produce the toxic principle (5) which can be present in the algae and in the water of mature cultures (6). The discovery of the toxin was fortuitous in the sense that AChR agonists do not have a (known) constructive function in the algae evolution of the synthetic pathway was likely a by-product of metabolic pathways in the algae. The compound became evident only through its toxic effects on other organisms. 

MARSOLAIS, F GIDDA, S.K., BOYD, J., VARIN, L Plant soluble sulfotransferases structural and functional similarity with mammalian enzymes. In Evolution of Metabolic Pathways (J.T. Romeo, R. Ibrahim, L. Varin, V. de Luca, eds.), Elsevier Science Ltd., Amsterdam. 2000, pp. 433-456. 

Volume 34 Evolution of Metabolic Pathways Proceedings of the Thirty-ninth Annual Meeting of the Phytochemical Society of North America, Montreal, Quebec, Canada, July, 1999... 

Stafford HA (2000) The evolution of phenolics in plants. In Romeo JT (ed) Evolution of metabolic pathways. Elsevier, New York, pp 25 17... 

In the above-mentioned examples, the prediction of CYP-mediated compound interactions is a starting point in any metabolic pathway prediction or enzyme inactivation. This chapter presents an evolution of a standard method [1], widely used in pharmaceutical research in the early-ADMET (absorption, distribution, metabolism, excretion and toxicity) field, which provides information on the biotransformations produced by CYP-mediated substrate interactions. The methodology can be applied automatically to all the cytochromes whose 3 D structure can be modeled or is known, including plants as well as phase II enzymes. It can be used by chemists to detect molecular positions that should be protected to avoid metabolic degradation, or to check the suitability of a new scaffold or prodrug. The fully automated procedure is also a valuable new tool in early-ADMET where metabolite- or mechanism based inhibition (MBI) must be evaluated as early as possible. 

An attractive hypothesis is the independent evolution in bacteria of their diffusible individualites and the currently recognized secondary metabolic pathways, in parallel with their surface components and their biosynthesis. An indicator for this would be the use of the same gene pool. The theory would include all substances that play a role in the build-up of glycan and other modified surface layers, lipids, murein, (glyco-) proteins (e.g., S-layers), polysaccharides, teichoic... 

Prescott, A.G., Two-oxoacid-dependant dioxygenases inefficient enzymes or evolutionary driving force, in Evolution of Metabolic Pathways, Romeo, J.T., Ibrahim, R., Varin, L., and De Luca, V., Eds., Elsevier Science, Oxford, 2000, 249. 

Tenser T, Gee DR. [2005). Modelling the evolution of secondary metabolic pathways. University of York, MPhil Project Report Abstract). Plants and microbes invest heavily in producing chemicals termed Natural Products. These chemicals are produced in secondary metabolic pathways. In this report, we develop a model for the evolution of secondary pathways, and investigate what factors are important in aUowing these pathways to arise and persist. The results imply that certain mutation rates are important in generating chemical diversity, and we give conditions on these for optimal fitness in a population. We also find that the rate of competitive evolution and the chances that new compounds have to be beneficial or harmful are important factors. 

In more extreme cases, the adaptive and reductive course of evolution led to permanent rejection of a number of metabolic pathways, including... 

A nearly universal set of several hundred small molecules is found in living cells the interconversions of these molecules in the central metabolic pathways have been conserved in evolution. 

Structural motifs become especially important in defining protein families and superfamilies. Improved classification and comparison systems for proteins lead inevitably to the elucidation of new functional relationships. Given the central role of proteins in living systems, these structural comparisons can help illuminate every aspect of biochemistry, from the evolution of individual proteins to the evolutionary history of complete metabolic pathways. 

S. Hettwer, M. Wilmanns, and R. Sterner, Directed evolution of a (beta alpha) (8)-barrel enzyme to catalyze related reactions in two different metabolic pathways, Proc. Natl. Acad. Sci. 2000, 97(18), 9925-9930. 

Retained substrate specificity (binding), changed chemistry A new enzyme evolves to supply substrate from an available precursor by evolution of enzyme using the substrate. The underlying hypothesis states that metabolic pathways evolve backwards A > 15 > C, 1 A >Pi is new, B >C is old enzyme ... 

Substrate specificity dominance The first and best known dominant mechanism in evolution concerns substrate specificity. The hypothesis underlying this mechanism states that metabolic pathways evolve backwards [Eq. (16.1), where Ej is the new enzyme and E2 is the old enzyme]. 

Taken together, these lines of evidence support the idea that evolution of metabolic pathways occurred after the introduction of atrazine (Shapir et al., 2007). Moreover, they may also indicate that certain use patterns of atrazine could potentially increase the ability of soil microorganisms to degrade the herbicide rapidly (Entry et al., 1995a Vanderheyden et al., 1997 Shaner and Henry, 2007). 

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