Integrated pathway engineering and transcriptome analysis for improved astaxanthin biosynthesis in Yarrowia lipolytica

整合途径工程和转录组分析以改善解脂耶氏酵母中的虾青素生物合成

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作者:Dan-Ni Wang, Jie Feng, Chen-Xi Yu, Xin-Kai Zhang, Jun Chen, Liu-Jing Wei, Zhijie Liu, Liming Ouyang, Lixin Zhang, Qiang Hua, Feng Liu

Abstract

Astaxanthin is a high value carotenoid with a broad range of commercial applications due to its superior antioxidant properties. In this study, β-carotene-producing Yarrowia lipolytica XK17 constructed in the lab was employed for astaxanthin biosynthesis. The catalytic effects of β-carotene ketolase CrtW and β-carotene hydroxylase CrtZ from various species were investigated. The PspCrtW from Paracoccus sp. and HpCrtZ# from Haematococcus pluvialis were confirmed to be the best combination in converting β-carotene. Several key bottlenecks in biomass and astaxanthin biosynthesis were effectively eliminated by optimizing the expression of the above enzymes and restoring uracil/leucine biosynthesis. In addition, the effects of astaxanthin biosynthesis on cell metabolism were investigated by integrated analysis of pathway modification and transcriptome information. After further optimization, strain DN30 was able to synthesize up to 730.3 mg/L astaxanthin in laboratory 5-L fermenter. This study provides a good metabolic strategy and a sustainable development platform for high-value carotenoid production.

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