scholarly journals Thailandamide, a Fatty Acid Synthesis Antibiotic That Is Coexpressed with a Resistant Target Gene

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Christopher E. Wozniak ◽  
Zhenjian Lin ◽  
Eric W. Schmidt ◽  
Kelly T. Hughes ◽  
Theodore G. Liou
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Target Gene ◽  
Gene Clusters ◽  
Acid Synthesis ◽  
Inducible Promoter ◽  
Content Type ◽  
Uncharacterized Gene ◽  
Fatty Acid Synthesis Pathway ◽  
Genetic Techniques

ABSTRACTMicrobes encode many uncharacterized gene clusters that may produce antibiotics and other bioactive small molecules. Methods for activating these genes are needed to explore their biosynthetic potential. A transposon containing an inducible promoter was randomly inserted into the genome of the soil bacteriumBurkholderia thailandensisto induce antibiotic expression. This screen identified the polyketide/nonribosomal peptide thailandamide as an antibiotic and discovered its regulator, AtsR. Mutants ofSalmonellaresistant to thailandamide had mutations in theaccAgene for acetyl coenzyme A (acetyl-CoA) carboxylase, which is one of the first enzymes in the fatty acid synthesis pathway. A second copy ofaccAin the thailandamide synthesis gene cluster keepsB. thailandensisresistant to its own antibiotic. These genetic techniques will likely be powerful tools for discovering other unusual antibiotics.

scholarly journals Genetic Regulation of the Bacterial Omega-3 Polyunsaturated Fatty Acid Biosynthesis Pathway

2020 ◽  
Vol 202 (16) ◽  
Author(s):  
Marco N. Allemann ◽  
Eric E. Allen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Genetic Regulation ◽  
Transcriptional Regulator ◽  
Acid Synthesis ◽  
Omega 3 ◽  
Content Type ◽  
Fatty Acid Synthesis Pathway ◽  
Long Chain

ABSTRACT A characteristic among many marine Gammaproteobacteria is the biosynthesis and incorporation of omega-3 polyunsaturated fatty acids into membrane phospholipids. The biosynthesis of eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) is mediated by a polyketide/fatty acid synthase mechanism encoded by a set of five genes, pfaABCDE. This unique fatty acid synthesis pathway coexists with the principal type II dissociated fatty acid synthesis pathway, which is responsible for the biosynthesis of core saturated, monounsaturated, and hydroxylated fatty acids used in phospholipid and lipid A biosynthesis. In this work, a genetic approach was undertaken to elucidate genetic regulation of the pfa genes in the model marine bacterium Photobacterium profundum SS9. Using a reporter gene fusion, we showed that expression of the pfa operon is downregulated in response to exogenous fatty acids, particularly long-chain monounsaturated fatty acids. This regulation occurs independently of the canonical fatty acid regulators, FabR and FadR, present in P. profundum SS9. Transposon mutagenesis and screening of a library of mutants identified a novel transcriptional regulator, which we have designated pfaF, to be responsible for the observed regulation of the pfa operon in P. profundum SS9. Gel mobility shift and DNase I footprinting assays confirmed that PfaF binds the pfaA promoter and identified the PfaF binding site. IMPORTANCE The production of long-chain omega-3 polyunsaturated fatty acids (PUFA) by marine Gammaproteobacteria, particularly those from deep-sea environments, has been known for decades. These unique fatty acids are produced by a polyketide-type mechanism and subsequently incorporated into the phospholipid membrane. While much research has focused on the biosynthesis genes, their products, and the phylogenetic distribution of these gene clusters, no prior studies have detailed the genetic regulation of this pathway. This study describes how this pathway is regulated under various culture conditions and has identified and characterized a fatty acid-responsive transcriptional regulator specific to PUFA biosynthesis.

scholarly journals Response of Fatty Acid Synthesis Genes to the Binding of Human Salivary Amylase by Streptococcus gordonii

2012 ◽  
Vol 78 (6) ◽  
pp. 1865-1875 ◽  
Author(s):  
Anna E. Nikitkova ◽  
Elaine M. Haase ◽  
M. Margaret Vickerman ◽  
Steven R. Gill ◽  
Frank A. Scannapieco
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Protein A ◽  
Acid Synthesis ◽  
Differentially Expressed ◽  
Streptococcus Gordonii ◽  
Bacterial Survival ◽  
Salivary Amylase ◽  
Content Type

ABSTRACTStreptococcus gordonii, an important primary colonizer of dental plaque biofilm, specifically binds to salivary amylase via the surface-associated amylase-binding protein A (AbpA). We hypothesized that a function of amylase binding toS. gordoniimay be to modulate the expression of chromosomal genes, which could influence bacterial survival and persistence in the oral cavity. Gene expression profiling by microarray analysis was performed to detect genes inS. gordoniistrain CH1 that were differentially expressed in response to the binding of purified human salivary amylase versus exposure to purified heat-denatured amylase. Selected genes found to be differentially expressed were validated by quantitative reverse transcription-PCR (qRT-PCR). Five genes from the fatty acid synthesis (FAS) cluster were highly (10- to 35-fold) upregulated inS. gordoniiCH1 cells treated with native amylase relative to those treated with denatured amylase. AnabpA-deficient strain ofS. gordoniiexposed to amylase failed to show a response in FAS gene expression similar to that observed in the parental strain. Predicted phenotypic effects of amylase binding toS. gordoniistrain CH1 (associated with increased expression of FAS genes, leading to changes in fatty acid synthesis) were noted; these included increased bacterial growth, survival at low pH, and resistance to triclosan. These changes were not observed in the amylase-exposedabpA-deficient strain, suggesting a role for AbpA in the amylase-induced phenotype. These results provide evidence that the binding of salivary amylase elicits a differential gene response inS. gordonii, resulting in a phenotypic adjustment that is potentially advantageous for bacterial survival in the oral environment.

Synthesis of [18F]fluoro-pivalic acid: an improved PET imaging probe for the fatty acid synthesis pathway in tumours

MedChemComm ◽  
2013 ◽  
Vol 4 (10) ◽  
pp. 1350 ◽  
Author(s):  
Federica Pisaneschi ◽  
Timothy H. Witney ◽  
Lisa Iddon ◽  
Eric O. Aboagye
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Pet Imaging ◽  
Acid Synthesis ◽  
Pivalic Acid ◽  
Imaging Probe ◽  
Fatty Acid Synthesis Pathway

scholarly journals Staphylococcus aureus Fatty Acid Auxotrophs Do Not Proliferate in Mice

2013 ◽  
Vol 57 (11) ◽  
pp. 5729-5732 ◽  
Author(s):  
Joshua B. Parsons ◽  
Matthew W. Frank ◽  
Jason W. Rosch ◽  
Charles O. Rock
Keyword(s):  
Fatty Acids ◽  
Staphylococcus Aureus ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Normal Growth ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Content Type

ABSTRACTInactivation of acetyl-coenzyme A (acetyl-CoA) carboxylase confers resistance to fatty acid synthesis inhibitors inStaphylococcus aureuson media supplemented with fatty acids. The addition ofanteiso-fatty acids (1 mM) plus lipoic acid supports normal growth of ΔaccDstrains, but supplementation with mammalian fatty acids was less efficient. Mice infected with strain RN6930 developed bacteremia, but bacteria were not detected in mice infected with its ΔaccDderivative.S. aureusbacteria lacking acetyl-CoA carboxylase can be propagatedin vitrobut were unable to proliferate in mice, suggesting that the acquisition of inactivating mutations in this enzyme is not a mechanism for the evasion of fatty acid synthesis inhibitors.

scholarly journals Fatty acid synthesis pathway provides lipid precursors for rhamnolipid biosynthesis in Burkholderia thailandensis E264

2018 ◽  
Vol 102 (14) ◽  
pp. 6163-6174 ◽  
Author(s):  
Victor U. Irorere ◽  
Thomas J. Smyth ◽  
Diego Cobice ◽  
Stephen McClean ◽  
Roger Marchant ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Burkholderia Thailandensis ◽  
Fatty Acid Synthesis Pathway

scholarly journals Taurine-Mediated IDOL Contributes to Resolution of Streptococcus uberis Infection

2021 ◽  
Vol 89 (5) ◽  
Author(s):  
Zhixin Wan ◽  
Riguo Lan ◽  
Yilin Zhou ◽  
Yuanyuan Xu ◽  
Zhenglei Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Bacterial Load ◽  
Critical Role ◽  
Acid Synthesis ◽  
Content Type ◽  
Streptococcus Uberis

ABSTRACT Metabolic alterations occur in pathogenic infections, but the role of lipid metabolism in the progression of bacterial mastitis is unclear. Cross talk between lipid droplets (LDs) and invading bacteria occurs, and targeting of de novo lipogenesis inhibits pathogen reproduction. In this study, we investigate the role(s) of lipid metabolism in mammary cells during Streptococcus uberis infection. Our results indicate that S. uberis induces the synthesis of fatty acids and production of LDs. Importantly, taurine reduces fatty acid synthesis, the abundance of LDs and the in vitro bacterial load of S. uberis. These changes are mediated, at least partly, by the E3 ubiquitin ligase IDOL, which is associated with the degradation of low-density lipoprotein receptors (LDLRs). We have identified a critical role for IDOL-mediated fatty acid synthesis in bacterial infection, and we suggest that taurine may be an effective prophylactic or therapeutic strategy for preventing S. uberis mastitis.

scholarly journals NovelXanthomonas campestrisLong-Chain-Specific 3-Oxoacyl-Acyl Carrier Protein Reductase Involved in Diffusible Signal Factor Synthesis

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Zhe Hu ◽  
Huijuan Dong ◽  
Jin-Cheng Ma ◽  
Yonghong Yu ◽  
Kai-Hui Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Xanthomonas Campestris ◽  
Octanoic Acid ◽  
Acyl Carrier Protein ◽  
Acid Synthesis ◽  
Carrier Protein ◽  
Content Type ◽  
Diffusible Signal Factor ◽  
Acyl Chains

ABSTRACTThe precursors of the diffusible signal factor (DSF) family signals ofXanthomonas campestrispv.campestrisare 3-hydroxyacyl-acyl carrier protein (3-hydroxyacyl-ACP) thioesters having acyl chains of 12 to 13 carbon atoms produced by the fatty acid biosynthetic pathway. We report a novel 3-oxoacyl-ACP reductase encoded by theX. campestrispv.campestrisXCC0416 gene (fabG2), which is unable to participate in the initial steps of fatty acyl synthesis. This was shown by the failure of FabG2 expression to allow growth at the nonpermissive temperature of anEscherichia colifabGtemperature-sensitive strain. However, when transformed into theE. colistrain together with a plasmid bearing theVibrio harveyiacyl-ACP synthetase gene (aasS), growth proceeded, but only when the medium contained octanoic acid.In vitroassays showed that FabG2 catalyzes the reduction of long-chain (≥C8) 3-oxoacyl-ACPs to 3-hydroxyacyl-ACPs but is only weakly active with shorter-chain (C4, C6) substrates. FabG1, the housekeeping 3-oxoacyl-ACP reductase encoded within the fatty acid synthesis gene cluster, could be deleted in a strain that overexpressedfabG2but only in octanoic acid-supplemented media. Growth of theX. campestrispv.campestrisΔfabG1strain overexpressingfabG2requiredfabHfor growth with octanoic acid, indicating that octanoyl coenzyme A is elongated byX. campestrispv.campestrisfabH. Deletion offabG2reduced DSF family signal production, whereas overproduction of either FabG1 or FabG2 in the ΔfabG2strain restored DSF family signal levels.IMPORTANCEQuorum sensing mediated by DSF signaling molecules regulates pathogenesis in several different phytopathogenic bacteria, includingXanthomonas campestrispv.campestris. DSF signaling also plays a key role in infection by the human pathogenBurkholderia cepacia. The acyl chains of the DSF molecules are diverted and remodeled from a key intermediate of the fatty acid synthesis pathway. We report aXanthomonas campestrispv.campestrisfatty acid synthesis enzyme, FabG2, of novel specificity that seems tailored to provide DSF signaling molecule precursors.

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