Identification of residues important for the catalysis, structure maintenance, and substrate specificity of yeast 3‐hydroxyacyl‐CoA dehydratase Phs1

Yazawa, Tomoyo; Naganuma, Tatsuro; Yamagata, Maki; Kihara, Akio

doi:10.1016/j.febslet.2013.02.006

Cited by 3 publications

(1 citation statement)

References 17 publications

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“…For instance, alignment of the homolog with the Phs1 protein sequence of S. cerevisiae reveals that all amino acid residues known to be important for function are conserved in the Sporobolomyces protein [[26], [27] Fig. S3].…”

Section: Resultsmentioning

confidence: 99%

Phs1 and the Synthesis of Very Long Chain Fatty Acids Are Required for Ballistospore Formation

et al. 2014

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The production and dissemination of spores by members of the fungal kingdom is a major reason for the success of this eukaryotic lineage in colonizing most terrestrial ecosystems. Ballistospores are a type of spore produced by basidiomycete fungi, such as the mushrooms and plant pathogenic rusts. These spores are forcefully discharged through a unique liquid-drop fusion mechanism, enabling the aerosolization of these particles that can contribute to plant disease and human allergies. The genes responsible for this process are unknown due to technical challenges in studying many of the fungi that produce ballistospores. Here, we applied newly-developed techniques in a forward genetic screen to identify genes required for ballistospore formation or function in a tractable red yeast, a species of Sporobolomyces. One strain bearing a mutation in the PHS1 gene was identified as a mirror mutant. PHS1 encodes 3-hydroxyacyl-CoA dehydratase required for the third step in very long chain fatty acid biosynthesis. The Sporobolomyces PHS1 gene complements the essential functions of a S. cerevisiae phs1 mutant. The Sporobolomyces phs1 mutant strain has less dehydratase activity and a reduction in very long chain fatty acids compared to wild type. The mutant strain also exhibits sensitivity to cell wall stress agents and loss of shooting due to a delay in ballistospore formation, indicating that the role of Phs1 in spore dissemination may be primarily in cellular integrity.

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Section: Resultsmentioning

confidence: 99%

Phs1 and the Synthesis of Very Long Chain Fatty Acids Are Required for Ballistospore Formation

et al. 2014

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Synthesis and degradation pathways, functions, and pathology of ceramides and epidermal acylceramides

Kihara

2016

Progress in Lipid Research

187

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The 3-hydroxyacyl-CoA dehydratases HACD1 and HACD2 exhibit functional redundancy and are active in a wide range of fatty acid elongation pathways

Sawai

Uchida

Ohno

et al. 2017

Journal of Biological Chemistry

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Differences among fatty acids (FAs) in chain length and number of double bonds create lipid diversity. FA elongation proceeds via a four-step reaction cycle, in which the 3-hydroxyacyl-CoA dehydratases (HACDs) HACD1-4 catalyze the third step. However, the contribution of each HACD to 3-hydroxyacyl-CoA dehydratase activity in certain tissues or in different FA elongation pathways remains unclear. is specifically expressed in muscles and is a myopathy-causative gene. Here, we generated KO mice and observed that these mice had reduced body and skeletal muscle weights. In skeletal muscle, mRNA expression was by far the highest among the However, we observed only an ∼40% reduction in HACD activity and no changes in membrane lipid composition in -KO skeletal muscle, suggesting that some HACD activities are redundant. Moreover, when expressed in yeast, both HACD1 and HACD2 participated in saturated and monounsaturated FA elongation pathways. Disruption of in the haploid human cell line HAP1 significantly reduced FA elongation activities toward both saturated and unsaturated FAs, and double disruption resulted in a further reduction. Overexpressed HACD3 exhibited weak activity in saturated and monounsaturated FA elongation pathways, and no activity was detected for HACD4. We therefore conclude that HACD1 and HACD2 exhibit redundant activities in a wide range of FA elongation pathways, including those for saturated to polyunsaturated FAs, with HACD2 being the major 3-hydroxyacyl-CoA dehydratase. Our findings are important for furthering the understanding of the molecular mechanisms in FA elongation and diversity.

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Identification of residues important for the catalysis, structure maintenance, and substrate specificity of yeast 3‐hydroxyacyl‐CoA dehydratase Phs1

Cited by 3 publications

References 17 publications

Phs1 and the Synthesis of Very Long Chain Fatty Acids Are Required for Ballistospore Formation

Phs1 and the Synthesis of Very Long Chain Fatty Acids Are Required for Ballistospore Formation

Synthesis and degradation pathways, functions, and pathology of ceramides and epidermal acylceramides

The 3-hydroxyacyl-CoA dehydratases HACD1 and HACD2 exhibit functional redundancy and are active in a wide range of fatty acid elongation pathways

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