FasR, a novel class of transcriptional regulator, governs the activation of fatty acid biosynthesis genes in <i>Streptomyces coelicolor</i>

Arabolaza, Ana; D’Angelo, Matilde; Comba, Santiago; Gramajo, Hugo

doi:10.1111/j.1365-2958.2010.07274.x

Cited by 37 publications

(41 citation statements)

References 63 publications

(93 reference statements)

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“…As a consequence, lower levels of FadR proteins also diminish the transcription from the fabH promoter (bottom). (14) bears some similarity to the activation of fabHDG by FadR described here for E. coli. Bacillus subtilis fab gene expression is also controlled by a transcription factor responsive to fatty acid levels, in this case, a repressor that responds to malonyl-CoA or malonyl-ACP (11).…”

Section: Discussionsupporting

confidence: 56%

“…In contrast, in Streptococcus pneumoniae, repression is caused by the presence of long-chain acyl-ACP (12). The repressor MabR regulates expression of the FASII genes in mycobacteria (13), whereas in Streptomyces coelicolor, the fab genes are regulated by an activator, FasR (14). In contrast to Gram-positive bacteria, it was thought previously that not all the fab genes in E. coli were controlled by fatty acid availability; rather, it was thought that regulation was restricted to unsaturated fatty acid biosynthesis by FadR and FabR regulation of only the fabA and fabB genes.…”

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confidence: 99%

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Transcription of the Escherichia coli Fatty Acid Synthesis OperonfabHDGIs Directly Activated by FadR and Inhibited by ppGpp

Rekoske

Lemke

et al. 2013

J Bacteriol

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bIn Escherichia coli, FadR and FabR are transcriptional regulators that control the expression of fatty acid degradation and unsaturated fatty acid synthesis genes, depending on the availability of fatty acids. In this report, we focus on the dual transcriptional regulator FadR. In the absence of fatty acids, FadR represses the transcription of fad genes required for fatty acid degradation. However, FadR is also an activator, stimulating transcription of the products of the fabA and fabB genes responsible for unsaturated fatty acid synthesis. In this study, we show that FadR directly activates another fatty acid synthesis promoter, PfabH, which transcribes the fabHDG operon, indicating that FadR is a global regulator of both fatty acid degradation and fatty acid synthesis. We also demonstrate that ppGpp and its cofactor DksA, known primarily for their role in regulation of the synthesis of the translational machinery, directly inhibit transcription from the fabH promoter. ppGpp also inhibits the fadR promoter, thereby reducing transcription activation of fabH by FadR indirectly. Our study shows that both ppGpp and FadR have direct roles in the control of fatty acid promoters, linking expression in response to both translation activity and fatty acid availability.

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Section: Discussionsupporting

confidence: 56%

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confidence: 99%

Transcription of the Escherichia coli Fatty Acid Synthesis OperonfabHDGIs Directly Activated by FadR and Inhibited by ppGpp

Rekoske

Lemke

et al. 2013

J Bacteriol

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“…The lipid transcriptional regulator FadR, a GntR family regulator, was first identified in E. coli (18,29). Other lipid transcriptional regulators recently reported include FasR of Streptomyces coelicolor (an activator of fatty acid biosynthesis) and MabR of M. tuberculosis (a repressor of genes in the cell wall mycolic acid biosynthesis pathway) (2,48). In both these bacteria, fatty acids produced in excess of the membrane phospholipid requirement may be diverted to storage granules (3,46,60).…”

Section: Discussionmentioning

confidence: 99%

Burkholderia cenocepacia ShvR-Regulated Genes That Influence Colony Morphology, Biofilm Formation, and Virulence

2011

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Burkholderia cenocepacia is an opportunistic pathogen that primarily infects cystic fibrosis (CF) patients. Previously, we reported that ShvR, a LysR regulator, influences colony morphology, virulence, and biofilm formation and regulates the expression of an adjacent 24-kb genomic region encoding 24 genes. In this study, we report the functional characterization of selected genes in this region. A Tn5 mutant with shiny colony morphology was identified with a polar mutation in BCAS0208, predicted to encode an acyl-coenzyme A dehydrogenase. Mutagenesis of BCAS0208 and complementation analyses revealed that BCAS0208 is required for rough colony morphology, biofilm formation, and virulence on alfalfa seedlings. It was not possible to complement with BCAS0208 containing a mutation in the catalytic site. BCAS0201, encoding a putative flavin adenine dinucleotide (FAD)-dependent oxidoreductase, and BCAS0207, encoding a putative citrate synthase, do not influence colony morphology but are required for optimum levels of biofilm formation and virulence. Both BCAS0208 and BCAS0201 contribute to pellicle formation, although individual mutations in each of these genes had no appreciable effect on pellicle formation. A mutant with a polar insertion in BCAS0208 was significantly less virulent in a rat model of chronic lung infection as well as in the alfalfa model. Genes in this region were shown to influence utilization of branched-chain fatty acids, tricarboxylic acid cycle substrates, L-arabinose, and branched-chain amino acids. Together, our data show that the ShvR-regulated genes BCAS0208 to BCAS0201 are required for the rough colony morphotype, biofilm and pellicle formation, and virulence in B. cenocepacia.

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“…This lipid yield was achieved after 6 to 7 days of cultivation in mineral salts medium (MSM) containing a limited nitrogen concentration of 0.025% (wt/vol) NH 4 Cl and 1% (wt/ vol) cellobiose. As is common for streptomycetes, the accumulated fatty acids of strain G25 were mostly long-chain, branched fatty acids (e.g., anteiso-C 15 or iso-C 16 ) and palmitate. These lipids could serve as feedstock for the production of partly branchedchain biodiesel with improved cold-temperature performance and stability properties (15).…”

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confidence: 92%

“…Most studies of streptomycete fatty acid synthesis (FAS)-which is closely linked to polyketide synthesis (PKS)-were conducted with S. coelicolor or S. glaucescens (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). These bacteria utilize the dissociated FAS II system and have a highly conserved fab gene cluster consisting of fabD, fabH, acpP, and fabF.…”

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confidence: 99%

Role of Wax Ester Synthase/Acyl Coenzyme A:Diacylglycerol Acyltransferase in Oleaginous Streptomyces sp. Strain G25

Röttig

Strittmatter

Schauer

et al. 2016

Appl Environ Microbiol

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Recently, we isolated a novel Streptomyces strain which can accumulate extraordinarily large amounts of triacylglycerol (TAG) and consists of 64% fatty acids (dry weight) when cultivated with glucose and 50% fatty acids (dry weight) when cultivated with cellobiose. To identify putative gene products responsible for lipid storage and cellobiose utilization, we analyzed its draft genome sequence. A single gene encoding a wax ester synthase/acyl coenzyme A (CoA):diacylglycerol acyltransferase (WS/DGAT) was identified and heterologously expressed in Escherichia coli. The purified enzyme Atf G25 showed acyltransferase activity with C 12 -or C 16 -acyl-CoA, C 12 to C 18 alcohols, or dipalmitoyl glycerol. This acyltransferase exhibits 24% amino acid identity to the model enzyme AtfA from Acinetobacter baylyi but has high sequence similarities to WS/DGATs from other Streptomyces species. To investigate the impact of Atf G25 on lipid accumulation, the respective gene, atf G25 , was inactivated in Streptomyces sp. strain G25. However, cells of the insertion mutant still exhibited DGAT activity and were able to store TAG, albeit in lower quantities and at lower rates than the wild-type strain. These findings clearly indicate that Atf G25 has an important, but not exclusive, role in TAG biosynthesis in the novel Streptomyces isolate and suggest the presence of alternative metabolic pathways for lipid accumulation which are discussed in the present study. IMPORTANCEA novel Streptomyces strain was isolated from desert soil, which represents an extreme environment with high temperatures, frequent drought, and nutrient scarcity. We believe that these harsh conditions promoted the development of the capacity for this strain to accumulate extraordinarily large amounts of lipids. In this study, we present the analysis of its draft genome sequence with a special focus on enzymes potentially involved in its lipid storage. Furthermore, the activity and importance of the detected acyltransferase were studied. As discussed in this paper, and in contrast to many other bacteria, streptomycetes seem to possess a complex metabolic network to synthesize lipids, whereof crucial steps are still largely unknown. This paper therefore provides insights into a range of topics, including extremophile bacteria, the physiology of lipid accumulation, and the biotechnological production of bacterial lipids. Even extreme environments, such as arid, desert-like regions, are populated by prokaryotes. These mostly Gram-positive bacteria are subjected to extreme fluctuations of temperature and water supply. In addition to desiccation and the resulting cellular damage, the bacteria frequently encounter nutrient limitation. To withstand these harsh environmental conditions, the majority of bacteria have evolved various strategies and are able to store lipophilic compounds such as polyhydroxyalkanoates (PHA), triacylglycerols (TAG), or wax esters (WE) (1-3). TAG are synthesized as primary storage compounds by many actinomycetes-which represent the pre...

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FasR, a novel class of transcriptional regulator, governs the activation of fatty acid biosynthesis genes in Streptomyces coelicolor

Cited by 37 publications

References 63 publications

Transcription of the Escherichia coli Fatty Acid Synthesis OperonfabHDGIs Directly Activated by FadR and Inhibited by ppGpp

Transcription of the Escherichia coli Fatty Acid Synthesis OperonfabHDGIs Directly Activated by FadR and Inhibited by ppGpp

Burkholderia cenocepacia ShvR-Regulated Genes That Influence Colony Morphology, Biofilm Formation, and Virulence

Role of Wax Ester Synthase/Acyl Coenzyme A:Diacylglycerol Acyltransferase in Oleaginous Streptomyces sp. Strain G25

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