Metabolic flux analysis of Escherichia coli MG1655 under octanoic acid (C8) stress

Fu, Yanfen; Yoon, Jong Moon; Jarboe, Laura R.; Shanks, Jacqueline V.

doi:10.1007/s00253-015-6387-6

Cited by 23 publications

(15 citation statements)

References 56 publications

(82 reference statements)

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“…It has been shown through metabolic flux analysis of E. coli under octanoic acid stress that carbon flux at the pyruvate node favors the NAD-independent PoxB-catalyzed pyruvate oxidation reaction to acetate, and a ubiquinol (Δ r G’°=−150 kJ/mol) instead of the NAD-dependent pyruvate decarboxylation reaction ( aceEF-lpd ) leading to acetyl-CoA, carbon dioxide, and NADH (Δ r G’°=-35 kJ/mol)[33,34]. The former reaction is more thermodynamically favorable compared to the latter as it produces acetate instead of acetyl-CoA.…”

Section: Systems-biology Analysis Confirms That Energy Metabolism Is mentioning

confidence: 99%

“…Increased expression of PoxB, strictly regulated by RpoS, may relieve oxidative stress in E. coli by reducing flux through the pyruvate dehydrogenase complex, which avoids the production of reactive oxygen species by NADH dehydrogenase[37]. This diverted flux reduces the carbon flow through the TCA cycle and reduces NADH production destined for the electron transport chain, increasing relative acetate production and greatly reducing biomass[34]. In acetate genomic library selections, increased biomass formation was associated with overexpression of regulated genes in the TCA cycle and biomass production pathways (e.g.…”

Section: Systems-biology Analysis Confirms That Energy Metabolism Is mentioning

confidence: 99%

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Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes

Sandoval

Papoutsakis

2016

Current Opinion in Microbiology

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Metabolite toxicity in microbes, particularly at the membrane, remains a bottleneck in the production of fuels and chemicals. Under chemical stress, native adaptation mechanisms combat hyper-fluidization by modifying the phospholipids in the membrane. Recent work in fluxomics reveals the mechanism of how membrane damage negatively affects energy metabolism while lipidomic and transcriptomic analyses show that strains evolved to be tolerant maintain membrane fluidity under stress through a variety of mechanisms such as incorporation of cyclopropanated fatty acids, trans-unsaturated fatty acids, and upregulation of cell wall biosynthesis genes. Engineered strains with modifications made in the biosynthesis of fatty acids, peptidoglycan, and lipopolysaccharide have shown increased tolerance to exogenous stress as well as increased production of desired metabolites of industrial importance. We review recent advances in elucidation of mechanisms or toxicity and tolerance as well as efforts to engineer the bacterial membrane and cell wall.

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Section: Systems-biology Analysis Confirms That Energy Metabolism Is mentioning

confidence: 99%

Section: Systems-biology Analysis Confirms That Energy Metabolism Is mentioning

confidence: 99%

Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes

Sandoval

Papoutsakis

2016

Current Opinion in Microbiology

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“…ILEs provide a definitive approach to trace the flow of carbon from substrates into unwanted byproducts and to detect when byproduct pathways become activated. For example, 13 C MFA recently identified increased acetate production and other flux shifts caused by accumulation of octanoic acid (C8) in the medium of E. coli cultures [46]. Based on these results, metabolic engineering strategies to divert carbon flux away from acetate production were proposed as a way to improve product yield and titer.…”

Section: Enhancing Product Yield By Identifying Wasteful Byproduct Pamentioning

confidence: 99%

Application of isotope labeling experiments and 13C flux analysis to enable rational pathway engineering

McAtee

Jazmin

Young

2015

Current Opinion in Biotechnology

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Isotope labeling experiments (ILEs) and (13)C flux analysis provide actionable information for metabolic engineers to identify knockout, overexpression, and/or media optimization targets. ILEs have been used in both academic and industrial labs to increase product formation, discover novel metabolic functions in previously uncharacterized organisms, and enhance the metabolic efficiency of host cell factories. This review highlights specific examples of how ILEs have been used in conjunction with enzyme or metabolic engineering to elucidate host cell metabolism and improve product titer, rate, or yield in a directed manner. We discuss recent progress and future opportunities involving the use of ILEs and (13)C flux analysis to characterize non-model host organisms and to identify and subsequently eliminate wasteful byproduct pathways or metabolic bottlenecks.

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“…In addition to elucidating the metabolic responses to the genetic modification of engineered E. coli strains, several 13 C-MFA studies have recently been performed on the metabolic responses to different environmental stresses on E. coli . First, 13 C-MFA was applied to elucidate the metabolic responses of E.coli to octanoic acid stress [ 37 ] ( Figure 3 ). A decreased flux in the TCA cycle and an increased flux in the pyruvate oxidative pathway for producing acetate were observed by comparing the flux distributions of stressed and unstressed E. coli strains.…”

Section: Integrating 13 C Metabolic Flux Analysmentioning

confidence: 99%

“…Microbial production of chemicals is more than the enzymatic conversion of the precursors to the products. Instead, to achieve the production of target chemicals at a high level, controls over microbial metabolism must coordinate the carbon flux [ 29 , 30 ], cofactor supply [ 31 , 32 , 33 ], cell maintenance [ 10 , 34 , 35 ], as well as other factors [ 36 , 37 , 38 , 39 ]. In general, many of the metabolic engineering strategies adopted to manipulate microbial metabolism for biochemical production only focus on a few known challenges (e.g., poor gene expression).…”

Section: Introductionmentioning

confidence: 99%

13C-Metabolic Flux Analysis: An Accurate Approach to Demystify Microbial Metabolism for Biochemical Production

2015

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Metabolic engineering of various industrial microorganisms to produce chemicals, fuels, and drugs has raised interest since it is environmentally friendly, sustainable, and independent of nonrenewable resources. However, microbial metabolism is so complex that only a few metabolic engineering efforts have been able to achieve a satisfactory yield, titer or productivity of the target chemicals for industrial commercialization. In order to overcome this challenge, 13C Metabolic Flux Analysis (13C-MFA) has been continuously developed and widely applied to rigorously investigate cell metabolism and quantify the carbon flux distribution in central metabolic pathways. In the past decade, many 13C-MFA studies have been performed in academic labs and biotechnology industries to pinpoint key issues related to microbe-based chemical production. Insightful information about the metabolic rewiring has been provided to guide the development of the appropriate metabolic engineering strategies for improving the biochemical production. In this review, we will introduce the basics of 13C-MFA and illustrate how 13C-MFA has been applied via integration with metabolic engineering to identify and tackle the rate-limiting steps in biochemical production for various host microorganisms

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Metabolic flux analysis of Escherichia coli MG1655 under octanoic acid (C8) stress

Cited by 23 publications

References 56 publications

Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes

Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes

Application of isotope labeling experiments and 13C flux analysis to enable rational pathway engineering

13C-Metabolic Flux Analysis: An Accurate Approach to Demystify Microbial Metabolism for Biochemical Production

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