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Significantly Enhanced Production of Patchoulol in Metabolically Engineered Saccharomyces cerevisiae
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2019-07-09 00:00:00 , DOI: 10.1021/acs.jafc.9b03456 Bin Ma 1 , Min Liu 1 , Zhen-Hai Li 1 , Xinyi Tao 1 , Dong-Zhi Wei 1 , Feng-Qing Wang 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2019-07-09 00:00:00 , DOI: 10.1021/acs.jafc.9b03456 Bin Ma 1 , Min Liu 1 , Zhen-Hai Li 1 , Xinyi Tao 1 , Dong-Zhi Wei 1 , Feng-Qing Wang 1
Affiliation
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Patchoulol, a natural sesquiterpene compound, is widely used in perfumes and cosmetics. Several strategies were adopted to enhance patchoulol production in Saccharomyces cerevisiae: (i) farnesyl pyrophosphate (FPP) synthase and patchoulol synthase were fused to increase the utilization of FPP precursor; (ii) expression of the limiting genes of the mevalonate pathway was enhanced; (iii) squalene synthase was weakened by a glucose-inducible promoter of HXT1 (promoter for hexose transporter) to reduce metabolic flux from FPP to ergosterol; and (iv) farnesol biosynthesis was inhibited to decrease the consumption of FPP. Glucose was used to balance the trade-off between the competitive squalene and patchoulol pathways. The patchoulol production was 59.2 ± 0.7 mg/L in a shaken flask with a final production of 466.8 ± 12.3 mg/L (20.5 ± 0.5 mg/g dry cell weight) combined with fermentation optimization, which was 7.8-fold higher than the reported maximum production. The work significantly promoted the industrialization process of patchoulol production using biobased microbial platforms.
中文翻译：
代谢工程改造的酿酒酵母中的广of香酚产量显着提高
广atch香酚，一种天然的倍半萜烯化合物，被广泛用于香水和化妆品中。采取了几种策略来提高啤酒酵母中广patch香酚的产生：（i）融合法呢基焦磷酸（FPP）合酶和广patch香合酶以增加FPP前体的利用率；（ii）增强了甲羟戊酸途径的限制性基因的表达；（iii）角鲨烯合酶被HXT1的葡萄糖诱导型启动子削弱（己糖转运蛋白的促进剂）以减少从FPP到麦角固醇的代谢通量；（iv）抑制了法尼醇的生物合成，从而降低了FPP的消耗量。葡萄糖被用来平衡角鲨烯和广oul香酚途径之间的权衡。摇瓶中的广patch香酚产量为59.2±0.7 mg / L，最终产量为466.8±12.3 mg / L（20.5±0.5 mg / g干细胞重量），并经过发酵优化，比报道的结果高7.8倍最高产量。这项工作大大促进了使用生物基微生物平台生产广patch香的工业化过程。
更新日期：2019-07-09
中文翻译：
代谢工程改造的酿酒酵母中的广of香酚产量显着提高
广atch香酚，一种天然的倍半萜烯化合物，被广泛用于香水和化妆品中。采取了几种策略来提高啤酒酵母中广patch香酚的产生：（i）融合法呢基焦磷酸（FPP）合酶和广patch香合酶以增加FPP前体的利用率；（ii）增强了甲羟戊酸途径的限制性基因的表达；（iii）角鲨烯合酶被HXT1的葡萄糖诱导型启动子削弱（己糖转运蛋白的促进剂）以减少从FPP到麦角固醇的代谢通量；（iv）抑制了法尼醇的生物合成，从而降低了FPP的消耗量。葡萄糖被用来平衡角鲨烯和广oul香酚途径之间的权衡。摇瓶中的广patch香酚产量为59.2±0.7 mg / L，最终产量为466.8±12.3 mg / L（20.5±0.5 mg / g干细胞重量），并经过发酵优化，比报道的结果高7.8倍最高产量。这项工作大大促进了使用生物基微生物平台生产广patch香的工业化过程。
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