The role of fluconazole in the regulation of fatty acid and unsaponifiable matter biosynthesis in Schizochytrium sp. MYA 1381
The role of fluconazole in the regulation of fatty acid and unsaponifiable matter biosynthesis in Schizochytrium sp. MYA 1381
复制标题
氟康唑在调节裂殖壶菌脂肪酸和不皂化物生物合成中的作用。
DOI：
10.1186/s12866-019-1622-4
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发表时间：
2019-11-15
期刊：
影响因子：
4.2
通讯作者：
Ling, Xueping
中科院分区：
文献类型：
--
作者：
Li, Jun;Zhou, Hao;Ling, Xueping
背景裂殖壶菌在工业上广泛用于合成多不饱和脂肪酸（PUFA），尤其是二十二碳六烯酸（DHA）。然而，PUFAs生物合成途径的不明确抑制了裂殖壶菌的进一步生产。甲羟戊酸途径产生的不皂化物（UM）对所有高等真核生物和微藻的细胞生长和细胞内代谢都至关重要。因此，裂殖壶菌UM生物合成的调控可能对脂肪酸的合成有重要影响。此外，众所周知，UM，如角鲨烯和β-胡萝卜素，具有很大的商业价值。因此，调节UM的生物合成也可能允许增加的价值ofSchizochytrium.ResultsTo调查UM的生物合成与脂肪酸积累在Schizochytrium的相关性，氟康唑被用来阻断甾醇途径。在48 h加入60 mg/L氟康唑使96 h的总脂（TL）增加了16%，但不影响细胞生长，并伴随着UMs和NADPH的显著变化。在72 h时，胆固醇含量降低了8%，角鲨烯含量提高了45%，这证明了氟康唑在抑制角鲨烯流向胆固醇方面的作用。作为另一种典型的具有抗氧化能力的UM，β-胡萝卜素产量在96 h时增加了53%。角鲨烯和β-胡萝卜素的增加可以增强细胞内的抗氧化能力，保护脂肪酸免受氧化。在96 h时，NADPH的含量比对照组高33%，说明细胞对脂肪酸的合成具有更强的还原能力。代谢分析进一步证实了裂殖壶菌中甾醇的调节与葡萄糖吸收、色素合成和脂肪酸的产生密切相关。结论本工作首次报道了裂殖壶菌中UM生物合成对脂肪酸积累的影响，发现UM通过改变裂殖壶菌细胞膜功能、胞内抗氧化能力和还原能力来影响脂肪酸的合成。我们相信，这项工作为改善微藻中的PUFA和其他有价值的物质提供了有价值的见解。
BackgroundSchizochytriumhas been widely used in industry for synthesizing polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA). However, unclear biosynthesis pathway of PUFAs inhibits further production of theSchizochytrium. Unsaponifiable matter (UM) from mevalonate pathway is crucial to cell growth and intracellular metabolism in all higher eukaryotes and microalgae. Therefore, regulation of UM biosynthesis inSchizochytriummay have important effects on fatty acids synthesis. Moreover, it is well known that UMs, such as squalene and β-carotene, are of great commercial value. Thus, regulating UM biosynthesis may also allow for an increased valuation ofSchizochytrium.ResultsTo investigate the correlation of UM biosynthesis with fatty acids accumulation inSchizochytrium,fluconazole was used to block the sterols pathway. The addition of 60 mg/L fluconazole at 48 h increased the total lipids (TLs) at 96 h by 16% without affecting cell growth, which was accompanied by remarkable changes in UMs and NADPH. Cholesterol content was reduced by 8%, and the squalene content improved by 45% at 72 h, which demonstrated fluconazole’s role in inhibiting squalene flow to cholesterol. As another typical UM with antioxidant capacity, the β-carotene production was increased by 53% at 96 h. The increase of squalene and β-carotene could boost intracellular oxidation resistance to protect fatty acids from oxidation. The NADPH was found to be 33% higher than that of the control at 96 h, which meant that the cells had more reducing power for fatty acid synthesis. Metabolic analysis further confirmed that regulation of sterols was closely related to glucose absorption, pigment biosynthesis and fatty acid production inSchizochytrium.ConclusionThis work first reported the effect of UM biosynthesis on fatty acid accumulation inSchizochytrium.The UM was found to affect fatty acid biosynthesis by changing cell membrane function, intracellular antioxidation and reducing power. We believe that this work provides valuable insights in improving PUFA and other valuable matters in microalgae.