Redirecting carbon flux into malonyl-CoA to improve resveratrol titers: Proof of concept for genetic interventions predicted by OptForce computational framework

2013 ◽  
Vol 103 ◽  
pp. 109-114 ◽  
Author(s):  
Namita Bhan ◽  
Peng Xu ◽  
Omar Khalidi ◽  
Mattheos A.G. Koffas
Keyword(s):  
Carbon Flux ◽  
Proof Of Concept ◽  
Computational Framework ◽  
Malonyl Coa ◽  
Genetic Interventions

scholarly journals Re-direction of carbon flux to key precursor malonyl-CoA via artificial small RNAs in photosynthetic Synechocystis sp. PCC 6803

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Sun ◽  
Shubin Li ◽  
Xinyu Song ◽  
Guangsheng Pei ◽  
Jinjin Diao ◽  
...  
Keyword(s):  
Carbon Flux ◽  
Small Rnas ◽  
Malonyl Coa ◽  
Synechocystis Sp ◽  
Pcc 6803

Genome-scale metabolic network modeling results in minimal interventions that cooperatively force carbon flux towards malonyl-CoA

2011 ◽  
Vol 13 (5) ◽  
pp. 578-587 ◽  
Author(s):  
Peng Xu ◽  
Sridhar Ranganathan ◽  
Zachary L. Fowler ◽  
Costas D. Maranas ◽  
Mattheos A.G. Koffas
Keyword(s):  
Metabolic Network ◽  
Carbon Flux ◽  
Network Modeling ◽  
Malonyl Coa ◽  
Metabolic Network Modeling ◽  
Genome Scale

scholarly journals Branch point control at malonyl-CoA node: A computational framework to uncover the design principles of an ideal genetic-metabolic switch

2019 ◽  
Author(s):  
Peng Xu
Keyword(s):  
Fatty Acids ◽  
Binding Affinity ◽  
Transcriptional Repressor ◽  
Design Principles ◽  
Optimal Controller ◽  
Metabolic Switch ◽  
Computational Framework ◽  
Target Molecule ◽  
Malonyl Coa ◽  
Metabolic Sink

AbstractLiving organism is an intelligent system encoded by hierarchically-organized information to perform precisely-controlled biological functions. Biophysical models are important tools to uncover the design rules underlying complex genetic-metabolic circuit interactions. Based on a previously engineered synthetic malonyl-CoA switch (Xu et al, PNAS 2014), we have formulated nine differential equations to unravel the design principles underlying an ideal metabolic switch to improve fatty acids production in E. coli. By interrogating the physiologically accessible parameter space, we have determined the optimal controller architecture to configure both the metabolic source pathway and metabolic sink pathway. We determined that low protein degradation rate, medium strength of metabolic inhibitory constant, high metabolic source pathway induction rate, strong binding affinity of the transcriptional activator toward the metabolic source pathway, weak binding affinity of the transcriptional repressor toward the metabolic sink pathway, and a strong cooperative interaction of transcriptional repressor toward metabolic sink pathway benefit the accumulation of the target molecule (fatty acids). The target molecule (fatty acid) production is increased from 50% to 10-folds upon application of the autonomous metabolic switch. With strong metabolic inhibitory constant, the system displays multiple steady states. Stable oscillation of metabolic intermediate is the driving force to allow the system deviate from its equilibrium state and permits bidirectional ON-OFF gene expression control, which autonomously compensates enzyme level for both the metabolic source and metabolic sink pathways. The computational framework may facilitate us to design and engineer predictable genetic-metabolic switches, quest for the optimal controller architecture of the metabolic source/sink pathways, as well as leverage autonomous oscillation as a powerful tool to engineer cell function.

scholarly journals Engineering acetyl-CoA metabolic shortcut for eco-friendly production of polyketides triacetic acid lactone in Yarrowia lipolytica

2019 ◽  
Author(s):  
Huan Liu ◽  
Monireh Marsafari ◽  
Fang Wang ◽  
Li Deng ◽  
Peng Xu
Keyword(s):  
Acetic Acid ◽  
Yarrowia Lipolytica ◽  
Carbon Flux ◽  
Oleaginous Yeast ◽  
Low Cost ◽  
Scale Production ◽  
Acetyl Coa ◽  
Malonyl Coa ◽  
Acid Lactone ◽  
Triacetic Acid Lactone

AbstractAcetyl-CoA is the central metabolic node connecting glycolysis, Krebs cycle and fatty acids synthase. Plant-derived polyketides, are assembled from acetyl-CoA and malonyl-CoA, represent a large family of biological compounds with diversified bioactivity. Harnessing microbial bioconversion is considered as a feasible approach to large-scale production of polyketides from renewable feedstocks. Most of the current polyketide production platform relied on the lengthy glycolytic steps to provide acetyl-CoA, which inherently suffers from complex regulation with metabolically-costly cofactor/ATP requirements. Using the simplest polyketide triacetic acid lactone (TAL) as a target molecule, we demonstrate that acetate uptake pathway in oleaginous yeast (Yarrowia lipolytica) could function as an acetyl-CoA shortcut to achieve metabolic optimality in producing polyketides. We identified the metabolic bottlenecks to rewire acetate utilization for efficient TAL production in Y. lipolytica, including generation of the driving force for acetyl-CoA, malonyl-CoA and NADPH. The engineered strain, with the overexpression of endogenous acetyl-CoA carboxylase (ACC1), malic enzyme (MAE1) and a bacteria-derived cytosolic pyruvate dehydrogenase (PDH), affords robust TAL production with titer up to 4.76 g/L from industrial glacier acetic acid in shake flasks, representing 8.5-times improvement over the parental strain. The acetate-to-TAL conversion ratio (0.149 g/g) reaches 31.9% of the theoretical maximum yield. The carbon flux through this acetyl-CoA metabolic shortcut exceeds the carbon flux afforded by the native acetyl-CoA pathways. Potentially, acetic acid could be manufactured in large-quantity at low-cost from Syngas fermentation or heterogenous catalysis (methanol carbonylation). This alternative carbon sources present a metabolic advantage over glucose to unleash intrinsic pathway limitations and achieve high carbon conversion efficiency and cost-efficiency. This work also highlights that low-cost acetic acid could be sustainably upgraded to high-value polyketides by oleaginous yeast species in an eco-friendly and cost-efficient manner.

Direct measurement of electron-diffraction-pattern intensities using an energy loss spectrometer

1989 ◽  
Vol 47 ◽  
pp. 668-669
Author(s):  
A. G. Jackson ◽  
M. Rowe
Keyword(s):  
Thermal Effects ◽  
Dynamic Range ◽  
Scattering Amplitude ◽  
Dynamical Theory ◽  
Site Symmetry ◽  
Proof Of Concept ◽  
Parallel Acquisition ◽  
Kinematic Approximation ◽  
Speed Up ◽  
Structure Calculations

Diffraction intensities from intermetallic compounds are, in the kinematic approximation, proportional to the scattering amplitude from the element doing the scattering. More detailed calculations have shown that site symmetry and occupation by various atom species also affects the intensity in a diffracted beam. [1] Hence, by measuring the intensities of beams, or their ratios, the occupancy can be estimated. Measurement of the intensity values also allows structure calculations to be made to determine the spatial distribution of the potentials doing the scattering. Thermal effects are also present as a background contribution. Inelastic effects such as loss or absorption/excitation complicate the intensity behavior, and dynamical theory is required to estimate the intensity value.The dynamic range of currents in diffracted beams can be 104or 105:1. Hence, detection of such information requires a means for collecting the intensity over a signal-to-noise range beyond that obtainable with a single film plate, which has a S/N of about 103:1. Although such a collection system is not available currently, a simple system consisting of instrumentation on an existing STEM can be used as a proof of concept which has a S/N of about 255:1, limited by the 8 bit pixel attributes used in the electronics. Use of 24 bit pixel attributes would easily allowthe desired noise range to be attained in the processing instrumentation. The S/N of the scintillator used by the photoelectron sensor is about 106 to 1, well beyond the S/N goal. The trade-off that must be made is the time for acquiring the signal, since the pattern can be obtained in seconds using film plates, compared to 10 to 20 minutes for a pattern to be acquired using the digital scan. Parallel acquisition would, of course, speed up this process immensely.

Remote Echocardiography: Proof of Concept for Support of National Disasters, Combat and Humanitarian Mission

2002 ◽  
Author(s):  
Sheri Yvonne Nottestad Boyd ◽  
Linda L. Huffer ◽  
Terry D. Bauch ◽  
James L. Furgerson
Keyword(s):  
Proof Of Concept ◽  
Humanitarian Mission

Model, simulation and experiments for a Buoyancy Organic Rankine Cycle

2020 ◽  
Vol 92 (1) ◽  
pp. 10906
Author(s):  
Jeroen Schoenmaker ◽  
Pâmella Gonçalves Martins ◽  
Guilherme Corsi Miranda da Silva ◽  
Julio Carlos Teixeira
Keyword(s):  
Model Simulation ◽  
Organic Rankine Cycle ◽  
Thermodynamic Cycle ◽  
Rankine Cycle ◽  
Test Body ◽  
Working Fluid ◽  
Proof Of Concept ◽  
Energy Scenario ◽  
New Type ◽  
Fluid Reservoir

Organic Rankine Cycle (ORC) systems are increasingly gaining relevance in the renewable and sustainable energy scenario. Recently our research group published a manuscript identifying a new type of thermodynamic cycle entitled Buoyancy Organic Rankine Cycle (BORC) [J. Schoenmaker, J.F.Q. Rey, K.R. Pirota, Renew. Energy 36, 999 (2011)]. In this work we present two main contributions. First, we propose a refined thermodynamic model for BORC systems accounting for the specific heat of the working fluid. Considering the refined model, the efficiencies for Pentane and Dichloromethane at temperatures up to 100 °C were estimated to be 17.2%. Second, we show a proof of concept BORC system using a 3 m tall, 0.062 m diameter polycarbonate tube as a column-fluid reservoir. We used water as a column fluid. The thermal stability and uniformity throughout the tube has been carefully simulated and verified experimentally. After the thermal parameters of the water column have been fully characterized, we developed a test body to allow an adequate assessment of the BORC-system's efficiency. We obtained 0.84% efficiency for 43.8 °C working temperature. This corresponds to 35% of the Carnot efficiency calculated for the same temperature difference. Limitations of the model and the apparatus are put into perspective, pointing directions for further developments of BORC systems.

Indocyanine green-augmented diode laser therapy of telangiectatic and reticular leg veins: a clinical proof-of-concept trial

2012 ◽  
Vol 25 (01) ◽  
Author(s):  
A Klein ◽  
G Shafirstein ◽  
E Kohl ◽  
W Bäumler ◽  
M Landthaler ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Laser Therapy ◽  
Diode Laser ◽  
Proof Of Concept

Evaluation einer als Proof-of-Concept entwickelten MRT-kompatiblen und röntgentransparenten Knochenbohrmaschine

2012 ◽  
Vol 184 (S 01) ◽  
Author(s):  
FV Güttler ◽  
K Winterwerber ◽  
C Gross ◽  
A Heinrich ◽  
M de Bucourt ◽  
...  
Keyword(s):  
Proof Of Concept
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