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通过代谢组学分析筛选苯甲酸衍生物的化学调节剂以改善SR21中的脂质积累。

Screening chemical modulators of benzoic acid derivatives to improve lipid accumulation in SR21 with metabolomics analysis.

作者信息

Li Zhipeng, Ling Xueping, Zhou Hao, Meng Tong, Zeng Jinjin, Hang Wei, Shi Yanyan, He Ning

机构信息

1Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 People's Republic of China.

2The Key Lab for Synthetic Biotechnology of Xiamen City, Xiamen University, Xiamen, 361005 People's Republic of China.

出版信息

Biotechnol Biofuels. 2019 Sep 4;12:209. doi: 10.1186/s13068-019-1552-2. eCollection 2019.

DOI:10.1186/s13068-019-1552-2
PMID:31508148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6724347/
Abstract

BACKGROUND

sp. is a marine fungus with great potential as an alternative commercial source of lipids rich in polyunsaturated fatty acids (PUFAs). To further increase lipid accumulation in sp., the effect of exogenous additives has become one of the hotspots of current research. Although benzoic acid derivatives showed positive effects on lipid accumulation in , the biochemical mechanism needs further investigation.

RESULTS

Four benzoic acid derivatives (sodium benzoate, -aminobenzoic acid, -methyl benzoic acid and folic acid) were screened and evaluated for their effect on lipid accumulation in SR21. The lipid yield was increased by 56.84% with -aminobenzoic acid (-ABA) at a concentration of 200 mg/L among the four tested chemical modulators. The metabolomics analysis showed that 200 mg/L -ABA was optimal for promoting glucose catabolism in glycolysis with an increase in the mevalonate pathway and a weakening of the tricarboxylic acid (TCA) cycle. Moreover, -ABA increased NADPH generation by enhancing the pentose phosphate pathway (PPP), ultimately redirecting the metabolic flux to lipid synthesis. Fed-batch fermentation further proved that -ABA could significantly increase the yield of lipid by 30.01%, reaching 99.67 g/L, and the lipid content was increased by 35.03%, reaching 71.12%. More importantly, the yields of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were increased by 33.28% and 42.0%, respectively.

CONCLUSION

The addition of -ABA could promote the synthesis of tetrahydrofolate, enhancing NADPH, which ultimately promoted the flow of carbon flux to lipid synthesis. These findings provide a valuable strategy for improving the lipid accumulation in by additives.

摘要

背景

某菌属是一种具有巨大潜力的海洋真菌,可作为富含多不饱和脂肪酸(PUFA)的脂质的替代商业来源。为了进一步提高某菌属中的脂质积累,外源添加剂的作用已成为当前研究的热点之一。尽管苯甲酸衍生物对某菌属中的脂质积累显示出积极作用,但其生化机制仍需进一步研究。

结果

筛选并评估了四种苯甲酸衍生物(苯甲酸钠、对氨基苯甲酸、对甲基苯甲酸和叶酸)对某菌属SR21脂质积累的影响。在四种测试的化学调节剂中,浓度为200mg/L的对氨基苯甲酸(-ABA)使脂质产量提高了56.84%。代谢组学分析表明,200mg/L的-ABA最适合促进糖酵解中的葡萄糖分解代谢,同时甲羟戊酸途径增加,三羧酸(TCA)循环减弱。此外,-ABA通过增强磷酸戊糖途径(PPP)增加了NADPH的生成,最终将代谢通量重定向到脂质合成。补料分批发酵进一步证明,-ABA可显著提高脂质产量30.01%,达到99.67g/L,脂质含量增加35.03%,达到71.12%。更重要的是,二十二碳六烯酸(DHA)和二十碳五烯酸(EPA)的产量分别提高了33.28%和42.0%。

结论

添加-ABA可促进四氢叶酸的合成,增强NADPH,最终促进碳通量流向脂质合成。这些发现为通过添加剂提高某菌属中的脂质积累提供了有价值的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/72eaf1b8d953/13068_2019_1552_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/871a9f6cd079/13068_2019_1552_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/97a0a5af0c29/13068_2019_1552_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/b2ddc479da26/13068_2019_1552_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/fed708c6e278/13068_2019_1552_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/274830ad07cb/13068_2019_1552_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/72eaf1b8d953/13068_2019_1552_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/871a9f6cd079/13068_2019_1552_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/97a0a5af0c29/13068_2019_1552_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/b2ddc479da26/13068_2019_1552_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/fed708c6e278/13068_2019_1552_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/274830ad07cb/13068_2019_1552_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76f/6724347/72eaf1b8d953/13068_2019_1552_Fig6_HTML.jpg

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