scholarly journals FADS Gene Cluster Polymorphisms: Important Modulators of Fatty Acid Levels and Their Impact on Atopic Diseases

2009 ◽  
Vol 2 (3) ◽  
pp. 119-128 ◽  
Author(s):  
Eva Lattka ◽  
Thomas Illig ◽  
Joachim Heinrich ◽  
Berthold Koletzko
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Woo Cheol Lee ◽  
Sungjae Choi ◽  
Ahjin Jang ◽  
Kkabi Son ◽  
Yangmee Kim

AbstractSome Gram-negative bacteria harbor lipids with aryl polyene (APE) moieties. Biosynthesis gene clusters (BGCs) for APE biosynthesis exhibit striking similarities with fatty acid synthase (FAS) genes. Despite their broad distribution among pathogenic and symbiotic bacteria, the detailed roles of the metabolic products of APE gene clusters are unclear. Here, we determined the crystal structures of the β-ketoacyl-acyl carrier protein (ACP) reductase ApeQ produced by an APE gene cluster from clinically isolated virulent Acinetobacter baumannii in two states (bound and unbound to NADPH). An in vitro visible absorption spectrum assay of the APE polyene moiety revealed that the β-ketoacyl-ACP reductase FabG from the A. baumannii FAS gene cluster cannot be substituted for ApeQ in APE biosynthesis. Comparison with the FabG structure exhibited distinct surface electrostatic potential profiles for ApeQ, suggesting a positively charged arginine patch as the cognate ACP-binding site. Binding modeling for the aryl group predicted that Leu185 (Phe183 in FabG) in ApeQ is responsible for 4-benzoyl moiety recognition. Isothermal titration and arginine patch mutagenesis experiments corroborated these results. These structure–function insights of a unique reductase in the APE BGC in comparison with FAS provide new directions for elucidating host–pathogen interaction mechanisms and novel antibiotics discovery.


2019 ◽  
Vol 122 (s1) ◽  
pp. S68-S79
Author(s):  
Cristina Martínez-Zaldívar ◽  
Hatim Azaryah ◽  
José A. García-Santos ◽  
Hans Demmelmair ◽  
Signe Altmäe ◽  
...  

AbstractVariants in the human genes of fatty acid (FA) desaturase 1 (FADS1), 2 (FADS2) and 3 (FADS3) are associated with PUFA blood levels. We explored if maternal prenatal supplementation and children’s genetic variation in seventeen SNP of the FADS1, FADS2 and FADS3 gene cluster influence twenty-one of the most relevant cheek cells’ derived FA in glycerophospholipids (GPL-FA). The study was conducted in 147 Spanish and German mother–children pairs participating in the Nutraceuticals for a Healthier Life (NUHEAL) study at 8, 9 and 9·5 years. Linear and mixed model longitudinal regression analyses were performed. Maternal fish-oil (FO) or FO+5-methyltetrahydrofolate (5-MTHF) supplementation during pregnancy was associated with a significant decrease of arachidonic acid (AA) concentrations in cheek cell GPL in the offspring, from 8 to 9·5 years; furthermore, maternal FO+5-MTHF supplementation was associated with higher n-6 docosapentaenoic acid concentrations in their children at age 8 years. FADS1 rs174556 polymorphism and different FADS2 genotypes were associated with higher concentrations of linoleic and α-linolenic acids in children; moreover, some FADS2 genotypes determined lower AA concentrations in children’s cheek cells. It is suggested an interaction between type of prenatal supplementation and the offspring genetic background driving GPL-FA levels at school age. Prenatal FO supplementation, and/or with 5-MTHF, seems to stimulate n-3 and n-6 FA desaturation in the offspring, increasing long-chain PUFA concentrations at school age, but depending on children’s FADS1 and FADS2 genotypes. These findings suggest potential early nutrition programming of FA metabolic pathways, but interacting with children’s FADS polymorphisms.


2019 ◽  
Vol 47 (2) ◽  
pp. 37-45
Author(s):  
Hiroto Kigoshi ◽  
Fuki Kawaguchi ◽  
Kenji Oyama ◽  
Hideyuki Mannen ◽  
Shinji Sasazaki

2009 ◽  
pp. no-no ◽  
Author(s):  
S. Zhang ◽  
T. J. Knight ◽  
J. M. Reecy ◽  
T. L. Wheeler ◽  
S. D. Shackelford ◽  
...  

Author(s):  
H. Fryssira ◽  
P. Makrythanasis ◽  
A. Kattamis ◽  
K. Stokidis ◽  
B. Menten ◽  
...  

2016 ◽  
Vol 46 (3) ◽  
pp. 461-471 ◽  
Author(s):  
E. Rucci ◽  
H. T. den Dekker ◽  
J. C. de Jongste ◽  
J. Steenweg-de-Graaff ◽  
R. Gaillard ◽  
...  

2019 ◽  
Vol 85 (22) ◽  
Author(s):  
Xiaopan Yang ◽  
Kunling Teng ◽  
Lili Li ◽  
Rina Su ◽  
Jie Zhang ◽  
...  

ABSTRACT Lactobacillus plantarum is a versatile bacterium with significant adaptability to harsh habitats containing excessive ethanol concentrations. It was found that the L. plantarum NF92-TetR/AcrR family regulator, AcrR, significantly enhanced the growth rate of this lactic acid bacterium in the presence of ethanol. Through screening 172 ethanol-resistant related genes by electrophoretic mobility shift and quantitative reverse transcription-PCR (RT-qPCR) assays, six genes were identified to be regulated by AcrR under ethanol stress. Among these was a gene coding for a 3-hydroxyacyl-ACP dehydratase (fabZ1) regulated by AcrR under ethanol stress. AcrR regulated fabZ1 under ethanol stress by binding to its promoter, PfabZ1. DNase I footprinting analysis indicated that there were two specific AcrR binding sites on PfabZ1. RT-PCR results showed fabZ1 could cotranscribe with its downstream 12 genes and conform a fatty acid de novo biosynthesis (fab) gene cluster under the control of PfabZ1. Both RT-qPCR of the fab gene cluster in acrR knockout and overexpression strains and fatty acid methyl ester analysis of the acrR knockout strain showed that AcrR could promote fatty acid synthesis in L. plantarum NF92. Membrane fluorescence anisotropy analysis of acrR knockout and overexpression strains showed that AcrR could increase membrane fluidity under ethanol stress. Thus, AcrR could regulate fatty acid synthesis and membrane fluidity to promote the adaption of L. plantarum NF92 to a high ethanol concentration. IMPORTANCE Ethanol tolerance is essential for L. plantarum strains living in substances with more than 9% ethanol, such as wine and beer. The details regarding how L. plantarum adapts to ethanol are still lacking. This study demonstrates that AcrR regulates the de novo synthesis of fatty acids in L. plantarum adapting to toxic levels of ethanol. We also identified the ability of the TetR/AcrR family regulator to bind to the fatty acid biosynthesis gene promoter, PfabZ1, in L. plantarum and defined the binding sites. This finding facilitates the induction of the adaptation of L. plantarum strains to ethanol for food fermentation applications.


2018 ◽  
Vol 85 (4) ◽  
Author(s):  
Jan Mareš ◽  
Jan Hájek ◽  
Petra Urajová ◽  
Andreja Kust ◽  
Jouni Jokela ◽  
...  

ABSTRACT Puwainaphycins (PUWs) and minutissamides (MINs) are structurally analogous cyclic lipopeptides possessing cytotoxic activity. Both types of compound exhibit high structural variability, particularly in the fatty acid (FA) moiety. Although a biosynthetic gene cluster responsible for synthesis of several PUW variants has been proposed in a cyanobacterial strain, the genetic background for MINs remains unexplored. Herein, we report PUW/MIN biosynthetic gene clusters and structural variants from six cyanobacterial strains. Comparison of biosynthetic gene clusters indicates a common origin of the PUW/MIN hybrid nonribosomal peptide synthetase and polyketide synthase. Surprisingly, the biosynthetic gene clusters encode two alternative biosynthetic starter modules, and analysis of structural variants suggests that initiation by each of the starter modules results in lipopeptides of differing lengths and FA substitutions. Among additional modifications of the FA chain, chlorination of minutissamide D was explained by the presence of a putative halogenase gene in the PUW/MIN gene cluster of Anabaena minutissima strain UTEX B 1613. We detected PUW variants bearing an acetyl substitution in Symplocastrum muelleri strain NIVA-CYA 644, consistent with an O-acetyltransferase gene in its biosynthetic gene cluster. The major lipopeptide variants did not exhibit any significant antibacterial activity, and only the PUW F variant was moderately active against yeast, consistent with previously published data suggesting that PUWs/MINs interact preferentially with eukaryotic plasma membranes. IMPORTANCE Herein, we deciphered the most important biosynthetic traits of a prominent group of bioactive lipopeptides. We reveal evidence for initiation of biosynthesis by two alternative starter units hardwired directly in the same gene cluster, eventually resulting in the production of a remarkable range of lipopeptide variants. We identified several unusual tailoring genes potentially involved in modifying the fatty acid chain. Careful characterization of these biosynthetic gene clusters and their diverse products could provide important insight into lipopeptide biosynthesis in prokaryotes. Some of the variants identified exhibit cytotoxic and antifungal properties, and some are associated with a toxigenic biofilm-forming strain. The findings may prove valuable to researchers in the fields of natural product discovery and toxicology.


2008 ◽  
Vol 101 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Peter Rzehak ◽  
Joachim Heinrich ◽  
Norman Klopp ◽  
Linda Schaeffer ◽  
Sebastian Hoff ◽  
...  

The present study gives further evidence for the recently found association between variants of the fatty acid desaturase 1 fatty acid desaturase 2 (FADS1 FADS2) gene cluster and PUFA in blood phospholipids and explores this association for cellular fatty acids in erythrocyte membranes. In a subgroup of adults participating in the Bavarian Nutrition Survey II, a cross-sectional population-based study conducted in Bavaria, Germany, allelic variation in three selected loci of the FADS1 FADS2 gene cluster was analysed and used for haplotype construction. Associations with plasma phospholipid PUFA (n 163) and PUFA in erythrocyte membranes (n 535) were investigated by regression analysis. All haplotypes of the original five-loci haplotypes of our previous study could be replicated. In addition, associations with serum phospholipid PUFA were confirmed in the present data set. Although less pronounced, associations between FADS1 FADS2 haplotypes and PUFA in erythrocyte membranes, particularly arachidonic and dihomo-γ-linolenic acid, could be established. We provide the first replication of the association of the FADS1 FADS2 gene cluster with PUFA in blood phospholipids. For the first time, such associations were also shown for PUFA in cell membranes.


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