Background: Metabolic pathways support the enzyme flux that converts input chemicals into energy and cellular building blocks. With a constant rate of input, steady-state flux is achieved when metabolite concentrations and reaction rates remain constant over time. Individual genes undergo mutation, while selection acts on higher level functions of the pathway, such as steady-state flux where applicable. Modeling the evolution of metabolic pathways through mechanistic sets of ordinary differential equations is a piece of the genotype-phenotype map model for interpreting genetic variation and inter-specific differences. Such models can generate distinct compensatory changes and adaptive changes from directional selection, indicating single nucleotide polymorphisms and fixed differences that could affect phenotype. If used for inference, this would ultimately enable detection of selection on metabolic pathways as well as inference of ancestral states for metabolic pathway function.
Results: A software tool for simulating the evolution of metabolic pathways based upon underlying biochemistry, phylogenetics, and evolutionary considerations is presented. The Python program, Phylogenetic Evolution of Metabolic Pathway Simulator (PEMPS), implements a mutation-selection framework to simulate the evolution of the pathway over a phylogeny by interfacing with COPASI to calculate the steady-state flux of the metabolic network, introducing mutations as alterations in parameter values according to a model, and calculating a fitness score and corresponding probability of fixation based on the change in steady-state flux value(s). Results from simulations are consistent with a priori expectations of fixation probabilities and systematic change in model parameters.
Conclusions: The PEMPS program simulates the evolution of a metabolic pathway with a mutation-selection modeling framework based on criteria like steady-state flux that is designed to work with SBML-formatted kinetic models, and Newick-formatted phylogenetic trees. The Python software is run on the Linux command line and is available at https://github.com/nmccloskey/PEMPS .
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http://dx.doi.org/10.1186/s12859-024-05867-7 | DOI Listing |
ACS Synth Biol
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College of Life Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271016, China.
Filamentous fungi are important cell factories for producing chemicals, organic acids, and enzymes. Although several genome editing tools are available for filamentous fungi, few effectively enable continuous evolution for rational engineering of complex phenotype. Here, we present CRISPR-Cas9 cytidine-base-editor (CBE) assisted evolution by continuously delivering a combinatorial sgRNA library to filamentous fungi.
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View Article and Find Full Text PDFWorld J Microbiol Biotechnol
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Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, 72 Binhai Road, Jimo, Qingdao, 266237, China.
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Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
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