Secretory and metabolic engineering of squalene in Yarrowia lipolytica.

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Tác giả: Liang Chai, Jiaxin Che, Jin Hou, Xiaoxu Liu, Qingsheng Qi, Zhengdong Wang

Ngôn ngữ: eng

Ký hiệu phân loại: 616.39 *Nutritional and metabolic diseases

Thông tin xuất bản: England : Bioresource technology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 642617

This short communication systematically explored ATP-binding cassette (ABC) transporters and developed a carrier protein-mediated metabolite trafficking system to engineer Yarrowia lipolytica for secretion of squalene. Specially, the squalene biosynthesis pathway was overexpressed to improve squalene production. Subsequently, a series of ABC transporters and oxysterol-binding proteins (OSH) were screened, with the combination of SNQ2 and OSH3 showing the most significant improvement in squalene secretion. Additionally, we designed a carrier protein-mediated metabolite trafficking system by fusing the binding domain of OSH3 with a secretion signal peptide. This approach, combined with the optimization of signal peptides, increased squalene secretion to 144.67 mg/L, which represented a 17-fold improvement over the initial strain. This system also demonstrated versatility by facilitating the extracellular export of β-carotene. In fed-batch cultivation, the engineered strain secreted 3.43 g/L of squalene extracellularly, accounting for 27.2 % of the total production. It represented the highest secretion level reported to date. This study establishes an efficient secretion platform for the transport of membrane-impermeable squalene in Y. lipolytica, providing valuable insights and strategies for the microbial production of terpenoids.
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