scholarly journals Studies of the Production of Fungal Polyketides in Aspergillus nidulans by Using Systems Biology Tools

2009 ◽  
Vol 75 (7) ◽  
pp. 2212-2220 ◽  
Author(s):  
Gianni Panagiotou ◽  
Mikael R. Andersen ◽  
Thomas Grotkjaer ◽  
Torsten B. Regueira ◽  
Jens Nielsen ◽  
...  
Keyword(s):  
Systems Biology ◽  
Metabolic Flux ◽  
Model Organism ◽  
Interaction Model ◽  
Chemical Diversity ◽  
Recombinant Strains ◽  
Production Platform ◽  
Depth Analysis ◽  
Penicillium Griseofulvum ◽  
High Yields

ABSTRACT Many filamentous fungi produce polyketide molecules with great significance as human pharmaceuticals; these molecules include the cholesterol-lowering compound lovastatin, which was originally isolated from Aspergillus terreus. The chemical diversity and potential uses of these compounds are virtually unlimited, and it is thus of great interest to develop a well-described microbial production platform for polyketides. Using genetic engineering tools available for the model organism Aspergillus nidulans, we constructed two recombinant strains, one expressing the Penicillium griseofulvum 6-methylsalicylic acid (6-MSA) synthase gene and one expressing the 6-MSA synthase gene and overexpressing the native xylulose-5-phosphate phosphoketolase gene (xpkA) for increasing the pool of polyketide precursor levels. The physiology of the recombinant strains and that of a reference wild-type strain were characterized on glucose, xylose, glycerol, and ethanol media in controlled bioreactors. Glucose was found to be the preferred carbon source for 6-MSA production, and 6-MSA concentrations up to 455 mg/liter were obtained for the recombinant strain harboring the 6-MSA gene. Our findings indicate that overexpression of xpkA does not directly improve 6-MSA production on glucose, but it is possible, if the metabolic flux through the lower part of glycolysis is reduced, to obtain quite high yields for conversion of sugar to 6-MSA. Systems biology tools were employed for in-depth analysis of the metabolic processes. Transcriptome analysis of 6-MSA-producing strains grown on glucose and xylose in the presence and absence of xpkA overexpression, combined with flux and physiology data, enabled us to propose an xpkA-msaS interaction model describing the competition between biomass formation and 6-MSA production for the available acetyl coenzyme A.

REPERTOIRE OF PROTEIN KINASES ENCODED IN THE GENOME OF ZEBRAFISH SHOWS REMARKABLY LARGE POPULATION OF PIM KINASES

2014 ◽  
Vol 12 (01) ◽  
pp. 1350014 ◽  
Author(s):  
R. RAKSHAMBIKAI ◽  
N. SRINIVASAN ◽  
RUPALI A. GADKARI
Keyword(s):  
Large Population ◽  
Model Organism ◽  
Tumor Formation ◽  
Detection Methods ◽  
Evolutionary Divergence ◽  
Homology Detection ◽  
Human Cancers ◽  
Pim Kinases ◽  
Depth Analysis ◽  
Almost All

In recent times, zebrafish has garnered lot of popularity as model organism to study human cancers. Despite high evolutionary divergence from humans, zebrafish develops almost all types of human tumors when induced. However, mechanistic details of tumor formation have remained largely unknown. Present study is aimed at analysis of repertoire of kinases in zebrafish proteome to provide insights into various cellular components. Annotation using highly sensitive remote homology detection methods revealed "substantial expansion" of Ser/Thr/Tyr kinase family in zebrafish compared to humans, constituting over 3% of proteome. Subsequent classification of kinases into subfamilies revealed presence of large number of CAMK group of kinases, with massive representation of PIM kinases, important for cell cycle regulation and growth. Extensive sequence comparison between human and zebrafish PIM kinases revealed high conservation of functionally important residues with a few organism specific variations. There are about 300 PIM kinases in zebrafish kinome, while human genome codes for only about 500 kinases altogether. PIM kinases have been implicated in various human cancers and are currently being targeted to explore their therapeutic potentials. Hence, in depth analysis of PIM kinases in zebrafish has opened up new avenues of research to verify the model organism status of zebrafish.

scholarly journals Probing Light-Dependent Regulation of the Calvin Cycle Using a Multi-Omics Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Nathaphon Yu King Hing ◽  
Uma K. Aryal ◽  
John A. Morgan
Keyword(s):  
Light Intensity ◽  
Atmospheric Carbon Dioxide ◽  
Metabolic Flux ◽  
Calvin Cycle ◽  
Model Organism ◽  
Flux Analysis ◽  
Photosynthetic Organisms ◽  
Light Intensities ◽  
External Conditions ◽  
Metabolite Channeling

Photoautotrophic microorganisms are increasingly explored for the conversion of atmospheric carbon dioxide into biomass and valuable products. The Calvin-Benson-Bassham (CBB) cycle is the primary metabolic pathway for net CO2 fixation within oxygenic photosynthetic organisms. The cyanobacteria, Synechocystis sp. PCC 6803, is a model organism for the study of photosynthesis and a platform for many metabolic engineering efforts. The CBB cycle is regulated by complex mechanisms including enzymatic abundance, intracellular metabolite concentrations, energetic cofactors and post-translational enzymatic modifications that depend on the external conditions such as the intensity and quality of light. However, the extent to which each of these mechanisms play a role under different light intensities remains unclear. In this work, we conducted non-targeted proteomics in tandem with isotopically non-stationary metabolic flux analysis (INST-MFA) at four different light intensities to determine the extent to which fluxes within the CBB cycle are controlled by enzymatic abundance. The correlation between specific enzyme abundances and their corresponding reaction fluxes is examined, revealing several enzymes with uncorrelated enzyme abundance and their corresponding flux, suggesting flux regulation by mechanisms other than enzyme abundance. Additionally, the kinetics of 13C labeling of CBB cycle intermediates and estimated inactive pool sizes varied significantly as a function of light intensity suggesting the presence of metabolite channeling, an additional method of flux regulation. These results highlight the importance of the diverse methods of regulation of CBB enzyme activity as a function of light intensity, and highlights the importance of considering these effects in future kinetic models.

scholarly journals The Detection of Early Epigenetic Inheritance of Mitochondrial Stress in C. Elegans with a Microfluidic Phenotyping Platform

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
H. B. Atakan ◽  
K. S. Hof ◽  
M. Cornaglia ◽  
J. Auwerx ◽  
M. A. M. Gijs
Keyword(s):  
Dna Sequence ◽  
Drug Exposure ◽  
Model Organism ◽  
Epigenetic Inheritance ◽  
Short Term ◽  
Mitochondrial Stress ◽  
New Device ◽  
C Elegans ◽  
Short Lifespan ◽  
Depth Analysis

AbstractFluctuations and deterioration in environmental conditions potentially have a phenotypic impact that extends over generations. Transgenerational epigenetics is the defined term for such intergenerational transient inheritance without an alteration in the DNA sequence. The model organism Caenorhabditis elegans is exceptionally valuable to address transgenerational epigenetics due to its short lifespan, well-mapped genome and hermaphrodite behavior. While the majority of the transgenerational epigenetics on the nematodes focuses on generations-wide heritage, short-term and in-depth analysis of this phenomenon in a well-controlled manner has been lacking. Here, we present a novel microfluidic platform to observe mother-to-progeny heritable transmission in C. elegans at high imaging resolution, under significant automation, and enabling parallelized studies. After approximately 24 hours of culture of L4 larvae under various concentrations and application periods of doxycycline, we investigated if mitochondrial stress was transferred from the mother nematodes to the early progenies. Automated and custom phenotyping algorithms revealed that a minimum doxycycline concentration of 30 µg/mL and a drug exposure time of 15 hours applied to the mothers could induce mitochondrial stress in first embryo progenies indeed, while this inheritance was not clearly observed later in L1 progenies. We believe that our new device could find further usage in transgenerational epigenetic studies modeled on C. elegans.

Applications of Metabolic Flux Balancing in Medicine

2009 ◽  
pp. 458-474
Author(s):  
Ferda Mavituna ◽  
Raul Munoz-Hernandez ◽  
Ana Katerine de Carvalho Lima Lobato
Keyword(s):  
Metabolic Engineering ◽  
Systems Biology ◽  
Metabolic Pathway ◽  
Metabolic Flux ◽  
Antibiotic Production ◽  
Computational Method ◽  
Future Trends ◽  
Stoichiometric Model ◽  
Cellular Pathways

This chapter summarizes the fundamentals of metabolic flux balancing as a computational tool of metabolic engineering and systems biology. It also presents examples from the literature for its applications in medicine. These examples involve mainly liver metabolism and antibiotic production. Metabolic flux balancing is a computational method for the determination of metabolic pathway fluxes through a stoichiometric model of the cellular pathways, using mass balances for intracellular metabolites. It is a powerful tool to study metabolism under normal and abnormal conditions with a view to engineer the metabolism. Its extended potential in medicine is emphasized in the future trends.

scholarly journals EcoCyc: fusing model organism databases with systems biology

2012 ◽  
Vol 41 (D1) ◽  
pp. D605-D612 ◽  
Author(s):  
Ingrid M. Keseler ◽  
Amanda Mackie ◽  
Martin Peralta-Gil ◽  
Alberto Santos-Zavaleta ◽  
Socorro Gama-Castro ◽  
...  
Keyword(s):  
Systems Biology ◽  
Model Organism ◽  
Model Organism Databases

scholarly journals Development of interaction model for air traffic controllers and pilots using discrete mathematics methods

2020 ◽  
Vol 23 (4) ◽  
pp. 72-83
Author(s):  
A. I. Stepnova ◽  
V. I. Kochergin ◽  
S. M. Stepanov ◽  
V. A. Borsoev
Keyword(s):  
Decision Making ◽  
Interaction Model ◽  
Air Traffic ◽  
Service Planning ◽  
Simulator Training ◽  
Discrete Mathematics ◽  
Air Traffic Controllers ◽  
Depth Analysis ◽  
The Impact ◽  
The Ideal

The purpose of the article is to create a database of errors and to develop an algorithm for a situational decision-making model taking into account availability of potential errors of air traffic controllers and pilots. Air traffic controllers and pilots typical errors were compiled and analyzed, arrays of specialists errors were created, binary error relations based on methods of discrete mathematics were also compiled in this article. This decision is caused by the need to formalize the interaction of specialists, since each error of the air traffic controller can be compared with a certain set of pilot errors and vice versa. In case of further in-depth analysis, it is possible to expand the database by adding additional errors arrays of the adjacent point controller, aerodrome service, planning service, etc. The goal is formed after analyzing the features of simulator training in higher educational institutions. The peculiarity is the absence of hazardous factors during the simulator training. This training takes place according to the ideal model. Undoubtedly, this approach is aimed at developing the correct algorithm of actions in normal or abnormal flight conditions, but thus the trainee can’t work out the decision-making skills if there is an error in the ideal algorithm. At the same time, existing specialists face unintended errors every working day, so having experience in this field plays an important role in minimizing the impact of the human factor on flight safety. In our case, it is proposed to include such a dangerous factor as an unintentional error in the joint training program for air traffic controllers and pilots, which will improve the training quality of specialists.

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