Magliano Pasqualina, Sanglard Dominique, Poirier Yves
Department of Plant Molecular Biology, University of Lausanne, CH-1015 Lausanne, Switzerland.
Biochim Biophys Acta. 2010 Dec;1801(12):1386-92. doi: 10.1016/j.bbalip.2010.08.008. Epub 2010 Aug 21.
The fungus Aspergillus nidulans contains both a mitochondrial and peroxisomal ß-oxidation pathway. This work was aimed at studying the influence of mutations in the foxA gene, encoding a peroxisomal multifunctional protein, or in the scdA/echA genes, encoding a mitochondrial short-chain dehydrogenase and an enoyl-CoA hydratase, respectively, on the carbon flux to the peroxisomal ß-oxidation pathway. A. nidulans transformed with a peroxisomal polyhydroxyalkanoate (PHA) synthase produced PHA from the polymerization of 3-hydroxyacyl-CoA intermediates derived from the peroxisomal ß-oxidation of external fatty acids. PHA produced from erucic acid or heptadecanoic acid contained a broad spectrum of monomers, ranging from 5 to 14 carbons, revealing that the peroxisomal ß-oxidation cycle can handle both long and short-chain intermediates. While the ∆foxA mutant grown on erucic acid or oleic acid synthesized 10-fold less PHA compared to wild type, the same mutant grown on octanoic acid or heptanoic acid produced 3- to 6-fold more PHA. Thus, while FoxA has an important contribution to the degradation of long-chain fatty acids, the flux of short-chain fatty acids to peroxisomal ß-oxidation is actually enhanced in its absence. While no change in PHA was observed in the ∆scdA∆echA mutant grown on erucic acid or oleic acid compared to wild type, there was a 2- to 4-fold increased synthesis of PHA in ∆scdA∆echA cells grown in octanoic acid or heptanoic acid. These results reveal that a compensatory mechanism exists in A. nidulans that increases the flux of short-chain fatty acids towards the peroxisomal ß-oxidation cycle when the mitochondrial ß-oxidation pathway is defective.
构巢曲霉含有线粒体和过氧化物酶体β-氧化途径。这项工作旨在研究编码过氧化物酶体多功能蛋白的foxA基因或分别编码线粒体短链脱氢酶和烯酰辅酶A水合酶的scdA/echA基因中的突变对过氧化物酶体β-氧化途径碳通量的影响。用一种过氧化物酶体聚羟基脂肪酸酯（PHA）合酶转化的构巢曲霉从外部脂肪酸过氧化物酶体β-氧化衍生的3-羟基酰基辅酶A中间体的聚合反应中产生PHA。由芥酸或十七烷酸产生的PHA包含范围从5到14个碳的广泛单体，这表明过氧化物酶体β-氧化循环可以处理长链和短链中间体。虽然在芥酸或油酸上生长的∆foxA突变体合成的PHA比野生型少10倍，但在辛酸或庚酸上生长的相同突变体产生的PHA多3至6倍。因此，虽然FoxA对长链脂肪酸的降解有重要贡献，但在其缺失时，短链脂肪酸向过氧化物酶体β-氧化的通量实际上会增强。与野生型相比，在芥酸或油酸上生长的∆scdA∆echA突变体中未观察到PHA的变化，但在辛酸或庚酸中生长的∆scdA∆echA细胞中PHA的合成增加了2至4倍。这些结果表明，构巢曲霉中存在一种补偿机制，当线粒体β-氧化途径有缺陷时，该机制会增加短链脂肪酸向过氧化物酶体β-氧化循环的通量。
