Hybrid of ant colony optimization and flux variability analysis for improving metabolites production

Metabolic engineering has been successfully used for the production of a variety of useful compounds such as L-phenylalanine and biohydrogen that received high demand on food, pharmaceutical, fossil fuels, and energy industries. Reaction deletion is one of the strategies of in silico metabolic engineering that can alter the metabolism of microbial cells with the objective to get the desired phenotypes. However, due to the size and complexity of metabolic networks, it is difficult to determine the near-optimal set of reactions to be knocked out. The complexity of the metabolic network is also caused by the presence of competing pathway that may interrupt the high production of a desireable metabolite. Consequently, this factor leads to low Biomass-Product Coupled Yield (BPCY), production rate and growth rate. Other than that, inefficiency of existing algorithms in modelling high growth rate and production rate is another problem that should be handled and solved. Therefore, this research proposed a hybrid algorithm comprising Ant Colony Optimization and Flux Variability Analysis (ACOFVA) to identify the best reaction combination to be knocked out to improve the production of desired metabolites in microorganisms. Based on the experimental results, ACOFVA shows an increase in terms of BPCY and production rate of L-Phenylalanine in Yeast and biohydrogen in Cyanobacteria, while maintaining the optimal growth rate for the target organism. Besides, suggested reactions to be knocked out for improving the production yield of L-Phenylalanine and biohydrogen have been identified and validated through the biological database. The algorithm also shows a good performance with better production rate and BPCY of L-Phenylalanine and biohydrogen than existing results

NIHBA : A network interdiction approach for metabolic engineering design

Funding Information: This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) for funding project ‘Synthetic Portabolomics: Leading the way at the crossroads of the Digital and the Bio Economies (EP/N031962/1)’. N.K. was funded by a Royal Academy of Engineering Chair in Emerging Technology award.Peer reviewedPublisher PD

Overview of Multiobjective Optimization Methods in in Silico Metabolic Engineering

Multiobjective optimization requires of finding a trade-off between multiple objectives. However, most of the objectives are contradict towards each other, thus makes it difficult for the traditional approaches to find a solution that satisfies all objectives. Fortunately, the problems are able to solve by the aid of Pareto methods. Meanwhile, in in silico Metabolic Engineering, the identification of reaction knockout strategies that produce mutant strains with a permissible growth rate and product rate of desired metabolites is still hindered. Previously, Evolutionary Algorithms (EAs) has been successfully used in determining the reaction knockout strategies. Nevertheless, most methods work by optimizing one objective function, which is growth rate or production rate. Furthermore, in bioprocesses, it involves multiple and conflicting objectives. In this review, we aim to show the different multiobjective evolutionary optimization methods developed for tackling the multiple and conflicting objectives in in silico metabolic engineering, as well as the approaches in multiobjective optimization

Microbial stress. From sensing to intracellular and population responses

We initially devised this Research Topic (RT) as a valuable initiative to collect high-quality scientific articles from the participants of the 4th European Federation of Biotechnology (EFB) Microbial Stress meeting held in Kinsale, Ireland, April 2018. The scope of the RT is based on the scientific content of that “Microbial Stress: from Systems to Molecules and back” meeting. Indeed, over 40% of the articles eventually accepted for publication were contributed by meeting participants, but notably the remaining 60% was contributed by authors that work in this field. The collection of 22 original research and 2 review articles, contributed by 163 authors collectively, deal with the many different aspects of the microbial responses to biotic and abiotic stresses, relevant to many fields: from host-pathogen interactions to biotechnology, from bioremediation to food processing, from molecular and single-cell to population studies. The RT showcases the rapid developments of the microbial stress research on a range of microorganisms and stress conditions, and confirms that understanding microbial physiology under stress can be a trigger for the development of new methodologies as well as helping to integrate the knowledge from many different microbiological fields of research. The retrospective analysis of the articles contributed to this RT allowed them to be assigned to one of four main sub-topics: (i) impact of weak organic acids and low pH on micro-organisms, from clinical to biotechnological contexts; (ii) adaptive responses in microbial pathogens to abiotic/environmental stress; (iii) oxidative and metal stress, from clinical to bioremediation contexts, and (iv) regulation of transcription and translation under stress, from epigenetic aspects to the role of second messengers and sRNA

Los receptores para el reconocimiento de patrones moleculares: aportaciones de la química computacional para el diseño de fármacos y la modulación de la inmunidad innata

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Química Orgánica y Farmacéutica, leída el 18/11/2019In this Thesis we have aimed the study of the molecular recognition processes of receptors involved in the innate immunity. More concretely, we have focused in two different types of lectins, Galectins and DC-SIGN, and in Toll-like receptor 4. We have made use of computational techniques, including docking and virtual screening, molecular dynamics simulations, conformational analysis and quantum mechanics calculations. The work has been organized into several chapters that are summarized as follows: Chapter 1 corresponds to the current knowledge and perspectives about receptors related to immunity, in particular: galectins, DC-SIGN, and Toll-like receptor 4, corresponding to the molecular recognition events and modulation by small molecules. Chapter 2 describes the state-of-the-art methods in molecular modeling and computational chemistry applied to the study of molecular recognition processes and drug design...En esta tesis hemos estudiado los procesos reconocimiento molecular de receptores involucrados en la inmunidad innata. Más concretamente, nos hemos centrado en dos tipos diferentes de lectinas, Galectinas y DC-SIGN, y en el receptor Toll-like 4 (TLR4). Hemos utilizado técnicas computacionales, incluyendo docking y cribado virtual, simulaciones de dinámica molecular, análisis conformacional y cálculos de mecánica cuántica. El trabajo se ha organizado en diferentes capítulos que se resumen como sigue: El capítulo 1 corresponde al estado del arte y las perspectivas relacionadas con los estudios de reconocimiento molecular proteína-carbohidrato y diseño de nuevos moduladores con actividad biológica en receptores de la inmunidad, en particular galectinas, DC-SIGN y el receptor Toll-like 4. El capítulo 2 describe el estado actual de los métodos en modelado molecular y química computacional aplicados al estudio de los procesos de reconocimiento molecular y diseño de fármacos...Fac. de FarmaciaTRUEunpu