Transcriptomic studies on the product stress response revealed that YCF1 is a beneficial factor for progesterone production in Yarrowia lipolytica

IF 4.4 2区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Synthetic and Systems Biotechnology Pub Date : 2025-04-17 DOI:10.1016/j.synbio.2025.04.008

Ying Wang , Ruosi Zhang , Mingdong Yao , Wenhai Xiao , Ying Wang , Ying-Jin Yuan

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Abstract

Progesterone is a widely used therapeutic hormone and a common precursor for the synthesis of pharmaceutical steroids in both mammals and plants. It has been successfully produced in heterologous microorganisms, but the market demand has not been met. The low progesterone yield, possibly due to product stress, may put pressure on the growth of strains and limit product synthesis efficiency. In this study, key pathways and genes that cause changes in amino acid and lipid metabolism and protein transport were identified through omics analysis. The expression of transporters leads to increased progesterone production and alleviated growth inhibition. Two related genes (gene IDs: 2912325 and 2908366) encoding the transporters glpF and SNQ2 improved production by 29.2 % and 51.7 %, respectively. Isoenzymes of native and exogenous transporters were screened and overexpressed. YCF1 from Saccharomyces cerevisiae exhibited the greatest benefit, increasing progesterone synthesis by 69.6 %. Our findings help reveal the impact of product stress on cellular metabolism and processes, providing research directions and literature support for the synthesis of other products.

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对产物胁迫反应的转录组学研究表明，YCF1是脂耶氏菌产生孕酮的有益因子

黄体酮是一种广泛使用的治疗激素，也是哺乳动物和植物合成药物类固醇的常见前体。它已成功地在异源微生物中生产，但尚未满足市场需求。黄体酮产率低，可能是由于产物应激造成的，可能对菌株的生长造成压力，限制产物的合成效率。本研究通过组学分析，确定了引起氨基酸、脂质代谢和蛋白质转运变化的关键途径和基因。转运蛋白的表达增加了孕酮的产生，减轻了生长抑制。编码转运体glpF和SNQ2的两个相关基因（基因id: 2912325和2908366）分别提高了29.2%和51.7%的产量。筛选原生和外源转运体的同工酶并过表达。从酿酒酵母中提取的YCF1获益最大，使黄体酮的合成增加了69.6%。我们的发现有助于揭示产物应激对细胞代谢和过程的影响，为其他产物的合成提供研究方向和文献支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Synthetic and Systems Biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-

CiteScore

6.90

自引率

12.50%

发文量

审稿时长

67 days

期刊介绍： Synthetic and Systems Biotechnology aims to promote the communication of original research in synthetic and systems biology, with strong emphasis on applications towards biotechnology. This journal is a quarterly peer-reviewed journal led by Editor-in-Chief Lixin Zhang. The journal publishes high-quality research; focusing on integrative approaches to enable the understanding and design of biological systems, and research to develop the application of systems and synthetic biology to natural systems. This journal will publish Articles, Short notes, Methods, Mini Reviews, Commentary and Conference reviews.