Localization of acyl carrier protein in Escherichia coli

Jackowski, Suzanne; Edwards, Harold H.; Davis, Daniel M.; Rock, Charles O.

doi:10.1128/jb.162.1.5-8.1985

Cited by 20 publications

(15 citation statements)

References 27 publications

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“…Under physiologic conditions, endogenous holo-mtACP was detected ( Fig 3B and C). In contrast, no endogenous apo-mtACP protein was visible, consistent with previous observations in other organisms that the inactive apo-mtACP form is not stable (Jackowski & Rock, 1983;Post-Beittenmiller et al, 1989).…”

Section: Resultssupporting

confidence: 91%

CoA‐dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases

Lambrechts

Schepers

et al. 2019

EMBO Mol Med

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PKAN, CoPAN, MePAN, and PDH‐E2 deficiency share key phenotypic features but harbor defects in distinct metabolic processes. Selective damage to the globus pallidus occurs in these genetic neurodegenerative diseases, which arise from defects in CoA biosynthesis (PKAN, CoPAN), protein lipoylation (MePAN), and pyruvate dehydrogenase activity (PDH‐E2 deficiency). Overlap of their clinical features suggests a common molecular etiology, the identification of which is required to understand their pathophysiology and design treatment strategies. We provide evidence that CoA‐dependent activation of mitochondrial acyl carrier protein (mtACP) is a possible process linking these diseases through its effect on PDH activity. CoA is the source for the 4′‐phosphopantetheine moiety required for the posttranslational 4′‐phosphopantetheinylation needed to activate specific proteins. We show that impaired CoA homeostasis leads to decreased 4′‐phosphopantetheinylation of mtACP. This results in a decrease of the active form of mtACP, and in turn a decrease in lipoylation with reduced activity of lipoylated proteins, including PDH. Defects in the steps of a linked CoA‐mtACP‐PDH pathway cause similar phenotypic abnormalities. By chemically and genetically re‐activating PDH, these phenotypes can be rescued, suggesting possible treatment strategies for these diseases.

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Section: Resultssupporting

confidence: 91%

CoA‐dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases

Lambrechts

Schepers

et al. 2019

EMBO Mol Med

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“…This suggests that, in the presence of saturating malonate concentrations, the in vivo activity of MatB (perhaps together with MatC) might be high enough to upset the delicate balance of intracellular CoASH and acyl‐CoA concentrations, thereby causing lethality. Similar observations have been made by other laboratories who have investigated Coenzyme A metabolism in E. coli (11, 12).…”

Section: Discussionsupporting

confidence: 88%

Enhancing the Atom Economy of Polyketide Biosynthetic Processes through Metabolic Engineering

Lombó

Pfeifer

Leaf³

et al. 2001

Biotechnol. Prog.

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Polyketides, a large family of bioactive natural products, are synthesized from building blocks derived from alpha-carboxylated Coenzyme A thioesters such as malonyl-CoA and (2S)-methylmalonyl-CoA. The productivity of polyketide fermentation processes in natural and heterologous hosts is frequently limited by the availability of these precursors in vivo. We describe a metabolic engineering strategy to enhance both the yield and volumetric productivity of polyketide biosynthesis. The genes matB and matC from Rhizobium trifolii encode a malonyl-CoA synthetase and a putative dicarboxylate transport protein, respectively. These proteins can directly convert exogenous malonate and methylmalonate into their corresponding CoA thioesters with an ATP requirement of 2 mol per mol of acyl-CoA produced. Heterologous expression of matBC in a recombinant strain of Streptomyces coelicolor that produces the macrolactone 6-deoxyerythronolide B results in a 300% enhancement of macrolactone titers. The unusual efficiency of the bioconversion is illustrated by the fact that approximately one-third of the methylmalonate units added to the fermentation medium are converted into macrolactones. The direct conversion of inexpensive feedstocks such as malonate and methylmalonate into polyketides represents the most carbon- and energy-efficient route to these high value natural products and has implications for cost-effective fermentation of numerous commercial and development-stage small molecules.

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“…The protein concentration of each sample was determined using the Bio‐Rad Protein Assay, and samples were stored at −20°C. To visualize the profile of intracellular acyl‐ACPs, 13% non‐denaturing gels were prepared, and urea was added to either 0.5 M or 2.5 M for SCFA or long‐chain fatty acid gels respectively (Rock and Cronan, 1981; Jackowski and Rock, 1983; Post‐Beittenmiller et al ., 1991). After electrophoresis in 192 mM glycine, 25 mM Tris buffer, samples were transferred to polyvinylidene difluoride membrane (Bio‐Rad), and the membranes blocked in TBS‐T (20 mM Tris‐HCl, pH 7.5, 500 mM NaCl, 0.05% Tween 20) containing 5% non‐fat milk.…”

Section: Methodsmentioning

confidence: 99%

“…To detect the L. pneumophila ACP proteins, the membranes were probed with a primary antibody generated by E. coli ACP (gift from C.O. Rock, Memphis, TN) diluted 1:500 and a secondary goat anti‐rabbit antibody conjugated to horseradish peroxidase (Pierce) diluted 1:8000 (Jackowski and Rock, 1983) and then developed with SuperSignal West Pico Chemiluminescent Substrate (Pierce).…”

Section: Methodsmentioning

confidence: 99%

Legionella pneumophila couples fatty acid flux to microbial differentiation and virulence

Edwards¹,

Dalebroux

Swanson

2009

Molecular Microbiology

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SummaryDuring its life cycle, Legionella pneumophila alternates between at least two phenotypes: a resilient, infectious form equipped for transmission and a replicative cell type that grows in amoebae and macrophages. Considering its versatility, we postulated that multiple cues regulate L. pneumophila differentiation. Beginning with a Biolog Phenotype MicroArray screen, we demonstrate that excess short-chain fatty acids (SCFAs) trigger replicative cells to cease growth and activate their panel of transmissive traits. To co-ordinate their response to SCFAs, L. pneumophila utilizes the LetA/LetS twocomponent system, but not phosphotransacetylase or acetyl kinase, two enzymes that generate highenergy phosphate intermediates. Instead, the stringent response enzyme SpoT appears to monitor fatty acid biosynthesis to govern transmission trait expression, as an altered distribution of acylated acyl carrier proteins correlated with the SpoT-dependent differentiation of cells treated with either excess SCFAs or the fatty acid biosynthesis inhibitors cerulenin and 5-(tetradecyloxy)-2-furoic acid. We postulate that, by exploiting the stringent response pathway to couple cellular differentiation to its metabolic state, L. pneumophila swiftly acclimates to stresses encountered in its host or the environment, thereby enhancing its overall fitness.

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Localization of acyl carrier protein in Escherichia coli

Cited by 20 publications

References 27 publications

CoA‐dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases

CoA‐dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases

Enhancing the Atom Economy of Polyketide Biosynthetic Processes through Metabolic Engineering

Legionella pneumophila couples fatty acid flux to microbial differentiation and virulence

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