scholarly journals Flux balance analysis predicts NADP phosphatase and NADH kinase are critical to balancing redox during xylose fermentation inScheffersomyces stipitis

2018 ◽  
Author(s):  
Kevin Correia ◽  
Anna Khusnutdinova ◽  
Peter Yan Li ◽  
Jeong Chan Joo ◽  
Greg Brown ◽  
...  
Keyword(s):  
Flux Balance Analysis ◽  
Xylose Fermentation ◽  
Xylose Reductase ◽  
Redox Metabolism ◽  
Reverse Engineer ◽  
Flux Balance ◽  
Substrate Preferences ◽  
Balance Analysis ◽  
Nadh Kinase

ABSTRACTXylose is the second most abundant sugar in lignocellulose and can be used as a feedstock for next-generation biofuels by industry.Saccharomyces cerevisiae, one of the main workhorses in biotechnology, is unable to metabolize xylose natively but has been engineered to ferment xylose to ethanol with the xylose reductase (XR) and xylitol dehydrogenase (XDH) genes fromScheffersoymces stipitis. In the scientific literature, the yield and volumetric productivity of xylose fermentation to ethanol in engineeredS. cerevisiaestill lagsS. stipitis, despite expressing of the same XR-XDH genes. These contrasting phenotypes can be due to differences inS. cerevisiae’sredox metabolism that hinders xylose fermentation, differences inS. stipitis’redox metabolism that promotes xylose fermentation, or both. To help elucidate howS. stipitisferments xylose, we used flux balance analysis to test various redox balancing mechanisms, reviewed published omics datasets, and studied the phylogeny of key genes in xylose fermentation.In vivoandin silicoxylose fermentation cannot be reconciled without NADP phosphatase (NADPase) and NADH kinase. We identified eight candidate genes for NADPase.PHO3.2was the sole candidate showing evidence of expression during xylose fermentation. Pho3.2p and Pho3p, a recent paralog, were purified and characterized for their substrate preferences. Only Pho3.2p was found to have NADPase activity. Both NADPase and NAD(P)H-dependent XR emerged from recent duplications in a common ancestor ofScheffersoymcesandSpathasporato enable efficient xylose fermentation to ethanol. This study demonstrates the advantages of using metabolic simulations, omics data, bioinformatics, and enzymology to reverse engineer metabolism.

Dynamic flux balance analysis of biomass and lipid production by Antarctic thraustochytrid Oblongichytrium sp. RT2316‐13

2020 ◽  
Vol 117 (10) ◽  
pp. 3006-3017 ◽  
Author(s):  
Carolina Shene ◽  
Paris Paredes ◽  
Liset Flores ◽  
Allison Leyton ◽  
Juan A. Asenjo ◽  
...  
Keyword(s):  
Flux Balance Analysis ◽  
Lipid Production ◽  
Dynamic Flux Balance Analysis ◽  
Flux Balance ◽  
Balance Analysis

scholarly journals Understanding the host-microbe interactions using metabolic modeling

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jack Jansma ◽  
Sahar El Aidy
Keyword(s):  
Human Health ◽  
Flux Balance Analysis ◽  
Bacterial Species ◽  
Flux Balance ◽  
Interaction Field ◽  
In Silico Simulation ◽  
Balance Analysis ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Genome Scale

AbstractThe human gut harbors an enormous number of symbiotic microbes, which is vital for human health. However, interactions within the complex microbiota community and between the microbiota and its host are challenging to elucidate, limiting development in the treatment for a variety of diseases associated with microbiota dysbiosis. Using in silico simulation methods based on flux balance analysis, those interactions can be better investigated. Flux balance analysis uses an annotated genome-scale reconstruction of a metabolic network to determine the distribution of metabolic fluxes that represent the complete metabolism of a bacterium in a certain metabolic environment such as the gut. Simulation of a set of bacterial species in a shared metabolic environment can enable the study of the effect of numerous perturbations, such as dietary changes or addition of a probiotic species in a personalized manner. This review aims to introduce to experimental biologists the possible applications of flux balance analysis in the host-microbiota interaction field and discusses its potential use to improve human health.

scholarly journals Why does yeast ferment? A flux balance analysis study

2010 ◽  
Vol 38 (5) ◽  
pp. 1225-1229 ◽  
Author(s):  
Evangelos Simeonidis ◽  
Ettore Murabito ◽  
Kieran Smallbone ◽  
Hans V. Westerhoff
Keyword(s):  
Flux Balance Analysis ◽  
Energy Cost ◽  
Yeast Fermentation ◽  
Minimal Amount ◽  
Aerobic Growth ◽  
Analysis Study ◽  
Flux Balance ◽  
Balance Analysis ◽  
Genome Scale ◽  
Excess Glucose

Advances in biological techniques have led to the availability of genome-scale metabolic reconstructions for yeast. The size and complexity of such networks impose limits on what types of analyses one can perform. Constraint-based modelling overcomes some of these restrictions by using physicochemical constraints to describe the potential behaviour of an organism. FBA (flux balance analysis) highlights flux patterns through a network that serves to achieve a particular objective and requires a minimal amount of data to make quantitative inferences about network behaviour. Even though FBA is a powerful tool for system predictions, its general formulation sometimes results in unrealistic flux patterns. A typical example is fermentation in yeast: ethanol is produced during aerobic growth in excess glucose, but this pattern is not present in a typical FBA solution. In the present paper, we examine the issue of yeast fermentation against respiration during growth. We have studied a number of hypotheses from the modelling perspective, and novel formulations of the FBA approach have been tested. By making the observation that more respiration requires the synthesis of more mitochondria, an energy cost related to mitochondrial synthesis is added to the FBA formulation. Results, although still approximate, are closer to experimental observations than earlier FBA analyses, at least on the issue of fermentation.

Critical assessment of genome-scale metabolic models of Arabidopsis thaliana

2022 ◽  
Author(s):  
Javad Zamani ◽  
Sayed-Amir Marashi ◽  
Tahmineh Lohrasebi ◽  
Mohammad-Ali Malboobi ◽  
Esmail Foroozan
Keyword(s):  
Arabidopsis Thaliana ◽  
Flux Balance Analysis ◽  
Critical Assessment ◽  
Flux Balance ◽  
Balance Analysis ◽  
Metabolic Models ◽  
Living Organisms ◽  
Genome Scale

Genome-scale metabolic models (GSMMs) have enabled researchers to perform systems-level studies of living organisms. As a constraint-based technique, flux balance analysis (FBA) aids computation of reaction fluxes and prediction of...

scholarly journals A simplified metabolic network reconstruction to promote understanding and development of flux balance analysis tools

2019 ◽  
Vol 105 ◽  
pp. 64-71 ◽  
Author(s):  
Kristopher D. Rawls ◽  
Bonnie V. Dougherty ◽  
Edik M. Blais ◽  
Ethan Stancliffe ◽  
Glynis L. Kolling ◽  
...  
Keyword(s):  
Metabolic Network ◽  
Flux Balance Analysis ◽  
Network Reconstruction ◽  
Metabolic Network Reconstruction ◽  
Flux Balance ◽  
Analysis Tools ◽  
Balance Analysis

scholarly journals Flux Balance Analysis of Mycolic Acid Pathway: Targets for Anti-tubercular Drugs

2005 ◽  
Vol preprint (2005) ◽  
pp. e46 ◽  
Author(s):  
Karthik Raman ◽  
Preethi Rajagopalan ◽  
Nagasuma Chandra
Keyword(s):  
Flux Balance Analysis ◽  
Mycolic Acid ◽  
Flux Balance ◽  
Balance Analysis ◽  
Acid Pathway
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