Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced β-Carotene Production in M. circinelloides CBS 277.49.
Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced β-Carotene Production in M. circinelloides CBS 277.49.
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DOI：
10.1155/2020/8890269
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发表时间：
2020
影响因子：
--
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Naz T;Nazir Y;Nosheen S;Ullah S;Halim H;Fazili ABA;Li S;Mustafa K;Mohamed H;Yang W;Song Y
微生物源产生的类胡萝卜素因其抗氧化和抗癌特性而具有重要的工业和药用价值。本研究采用响应面法（RSM）对圆形圆霉菌株277.49的β-胡萝卜素产量进行了优化。用蓝草蛋白和酮康唑分别抑制脂肪酸和甾醇生物合成途径，通过将代谢池转向甲羟戊酸途径来促进β-胡萝卜素的产生。筛选实验中使用的所有三个变量都被发现对β-胡萝卜素的产生具有重要意义。采用RSM中心复合设计，进一步评价C/N比、蓝蓝蛋白和酮康唑的协同效应，优化其β-胡萝卜素产量。我们的研究结果发现，不同浓度的C/N比、蓝蓝蛋白和酮康唑的协同组合显著影响了β-胡萝卜素的产量。以C/N 25、10 μg/mL蓝绿素和150 mg/L酮康唑为最佳培养基（标准11），最大β-胡萝卜素产量为4.26 mg/L (0.43 mg/g)，比未优化培养基（1.68 mg/L, 0.17 mg/g）提高了157%。因此，我们得出结论，代谢通量已成功地重定向到甲羟戊酸途径，以促进CBS 277.49中β-胡萝卜素的产生。
Carotenoids produced by microbial sources are of industrial and medicinal importance due to their antioxidant and anticancer properties. In the current study, optimization of β-carotene production in M. circinelloides strain 277.49 was achieved using response surface methodology (RSM). Cerulenin and ketoconazole were used to inhibit fatty acids and the sterol biosynthesis pathway, respectively, in order to enhance β-carotene production by diverting metabolic pool towards the mevalonate pathway. All three variables used in screening experiments were found to be significant for the production of β-carotene. The synergistic effect of the C/N ratio, cerulenin, and ketoconazole was further evaluated and optimized for superior β-carotene production using central composite design of RSM. Our results found that the synergistic combination of C/N ratios, cerulenin, and ketoconazole at different concentrations affected the β-carotene productions significantly. The optimal production medium (std. order 11) composed of C/N 25, 10 μg/mL cerulenin, and 150 mg/L ketoconazole, producing maximum β-carotene of 4.26 mg/L (0.43 mg/g) which was 157% greater in comparison to unoptimized medium (1.68 mg/L, 0.17 mg/g). So, it was concluded that metabolic flux had been successfully redirected towards the mevalonate pathway for enhanced β-carotene production in CBS 277.49.
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