Futile Cycling of Intermediates of Fatty Acid Biosynthesis toward Peroxisomal β-Oxidation in Saccharomyces cerevisiae

Marchesini, Silvia; Poirier, Yves

doi:10.1074/jbc.m305574200

Cited by 40 publications

(26 citation statements)

References 33 publications

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“…When the mcl-PHA polymerase was targeted to the peroxisomes as previously done by Marchesini and Poirier (18), the yeast accumulated PHA to approximately 0.13% of the CDW. The PHA was composed of C 12 , C 10 , and C 8 monomers, with the C 12 monomers representing the largest fraction, confirming data presented by Marchesini and Poirier (18). Since complete ␤-oxidation is not possible in the fox3 mutant, the C 8 -C 10 precursors are likely derived from fatty acid biosynthesis.…”

Section: Resultssupporting

confidence: 74%

“…Another alternative carbon source for PHA precursors is fatty acids biosynthesis (18). When the pex5 mutant was grown in medium containing only glycerol, C 8 and C 6 monomers were detected in the synthesized PHA.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, when undecanoic acid was used as the carbon source, in addition to odd-chain-length PHAs, even-chain PHA monomers including C 12 , C 10 , C 8 , and C 6 were detected. These even-chain precursors may originate from fatty acid biosynthesis, as proposed by Marchesini and Poirier (18). When the pex5 mutant was grown in medium containing glycerol and oleic acid or only glycerol, the culture accumulated PHA composed of C 8 and C 6 monomers.…”

Section: Downloaded Frommentioning

confidence: 98%

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Engineering the Monomer Composition of Polyhydroxyalkanoates Synthesized in Saccharomyces cerevisiae

Zhang

Carlson

Srienc

2006

Appl Environ Microbiol

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Polyhydroxyalkanoates (PHAs) have received considerable interest as renewable-resource-based, biodegradable, and biocompatible plastics with a wide range of potential applications. We have engineered the synthesis of PHA polymers composed of monomers ranging from 4 to 14 carbon atoms in either the cytosol or the peroxisome of Saccharomyces cerevisiae by harnessing intermediates of fatty acid metabolism. Cytosolic PHA production was supported by establishing in the cytosol critical ␤-oxidation chemistries which are found natively in peroxisomes. This platform was utilized to supply medium-chain (C 6 to C 14 ) PHA precursors from both fatty acid degradation and synthesis to a cytosolically expressed medium-chain-length (mcl) polymerase from Pseudomonas oleovorans. Synthesis of short-chain-length PHAs (scl-PHAs) was established in the peroxisome of a wild-type yeast strain by targeting the Ralstonia eutropha scl polymerase to the peroxisome. This strain, harboring a peroxisomally targeted scl-PHA synthase, accumulated PHA up to approximately 7% of its cell dry weight. These results indicate (i) that S. cerevisiae expressing a cytosolic mcl-PHA polymerase or a peroxisomal scl-PHA synthase can use the 3-hydroxyacyl coenzyme A intermediates from fatty acid metabolism to synthesize PHAs and (ii) that fatty acid degradation is also possible in the cytosol as ␤-oxidation might not be confined only to the peroxisomes. Polymers of even-numbered, odd-numbered, or a combination of even-and odd-numbered monomers can be controlled by feeding the appropriate substrates. This ability should permit the rational design and synthesis of polymers with desired material properties.

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Section: Resultssupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 98%

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Engineering the Monomer Composition of Polyhydroxyalkanoates Synthesized in Saccharomyces cerevisiae

Zhang

Carlson

Srienc

2006

Appl Environ Microbiol

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“…3). Interestingly, short-and medium-chain fatty acids that are prematurely released from fatty acid synthase are directed toward the peroxisomal ␤-oxidation pathway in S. cerevisiae (25). those used for microarray analysis.…”

Section: Figmentioning

confidence: 99%

A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis

Tripathi

Feng

et al. 2012

Antimicrob Agents Chemother

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c 6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model yeast Saccharomyces cerevisiae to investigate its mechanism of action. 6-NDA elicited a transcriptome response indicative of fatty acid stress, altering the expression of genes that are required for yeast growth in the presence of oleate. Mutants of S. cerevisiae lacking transcription factors that regulate fatty acid ␤-oxidation showed increased sensitivity to 6-NDA. Fatty acid profile analysis indicated that 6-NDA inhibited the formation of fatty acids longer than 14 carbons in length. In addition, the growth inhibitory effect of 6-NDA was rescued in the presence of exogenously supplied oleate. To investigate the response of a pathogenic fungal species to 6-NDA, transcriptional profiling and biochemical analyses were also conducted in C. albicans. The transcriptional response and fatty acid profile of C. albicans were comparable to those obtained in S. cerevisiae, and the rescue of growth inhibition with exogenous oleate was also observed in C. albicans. In a fluconazole-resistant clinical isolate of C. albicans, a fungicidal effect was produced when fluconazole was combined with 6-NDA. In hyphal growth assays, 6-NDA inhibited the formation of long hyphal filaments in C. albicans. Collectively, our results indicate that the antifungal activity of 6-NDA is mediated by a disruption in fatty acid homeostasis and that 6-NDA has potential utility in the treatment of superficial Candida infections.

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“…During alcoholic fermentation, short-chain fatty acid and MCFA intermediates are prematurely released from the cytoplasmic fatty acid synthase (FAS) complex (21,37). Because MCFAs are synthesized in the FAS complex, it is likely that the control mechanisms operating on fatty acid synthesis are also involved in control of MCFA formation.…”

mentioning

confidence: 99%

Parameters Affecting Ethyl Ester Production bySaccharomyces cerevisiaeduring Fermentation

Saerens

Verstrepen

Dijck

et al. 2008

Appl Environ Microbiol

416

260

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Volatile esters are responsible for the fruity character of fermented beverages and thus constitute a vital group of aromatic compounds in beer and wine. Many fermentation parameters are known to affect volatile ester production. In order to obtain insight into the production of ethyl esters during fermentation, we investigated the influence of several fermentation variables. A higher level of unsaturated fatty acids in the fermentation medium resulted in a general decrease in ethyl ester production. On the other hand, a higher fermentation temperature resulted in greater ethyl octanoate and decanoate production, while a higher carbon or nitrogen content of the fermentation medium resulted in only moderate changes in ethyl ester production. Analysis of the expression of the ethyl ester biosynthesis genes EEB1 and EHT1 after addition of medium-chain fatty acid precursors suggested that the expression level is not the limiting factor for ethyl ester production, as opposed to acetate ester production. Together with the previous demonstration that provision of mediumchain fatty acids, which are the substrates for ethyl ester formation, to the fermentation medium causes a strong increase in the formation of the corresponding ethyl esters, this result further supports the hypothesis that precursor availability has an important role in ethyl ester production. We concluded that, at least in our fermentation conditions and with our yeast strain, the fatty acid precursor level rather than the activity of the biosynthetic enzymes is the major limiting factor for ethyl ester production. The expression level and activity of the fatty acid biosynthetic enzymes therefore appear to be prime targets for flavor modification by alteration of process parameters or through strain selection.During fermentation the yeast Saccharomyces cerevisiae produces a broad range of aroma-active substances, which are vital for the complex flavor of fermented beverages, such as beer and wine. In particular, volatile esters are of major industrial interest because the presence of these compounds determines the fruity aroma of beer and wine (6,7,9,20,24,26,27,30,31,36). Even small changes in the concentrations of these secondary metabolites can have large effects on the final sensorial quality of fermented beverages. There are two main groups of flavor-active esters in fermented beverages. The first group contains the acetate esters (in which the acid group is acetate and the alcohol group is ethanol or a complex alcohol derived from amino acid metabolism), such as ethyl acetate (solventlike aroma), isoamyl acetate (banana aroma), and phenyl ethyl acetate (roses, honey). The second group is the ethyl esters (in which the alcohol group is ethanol and the acid group is a medium-chain fatty acid [MCFA]) and includes ethyl hexanoate (anise seed, applelike aroma), ethyl octanoate (sour apple aroma), and ethyl decanoate (floral odor). Of these two groups, the acetate esters have received the most attention, not because they are more important but because ...

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Futile Cycling of Intermediates of Fatty Acid Biosynthesis toward Peroxisomal β-Oxidation in Saccharomyces cerevisiae

Cited by 40 publications

References 33 publications

Engineering the Monomer Composition of Polyhydroxyalkanoates Synthesized in Saccharomyces cerevisiae

Engineering the Monomer Composition of Polyhydroxyalkanoates Synthesized in Saccharomyces cerevisiae

A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis

Parameters Affecting Ethyl Ester Production bySaccharomyces cerevisiaeduring Fermentation

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