非还原聚基合成酶之间的代谢竞争推动了深海真菌Talaromyces radicus中隐藏的化学多样性
Jun Wu1, Wei-Chen Chen1,2, Bowei Wen3,4
1Department of Radiation and Medical Oncology, Zhongnan Hospital, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
Organic letters
|January 29, 2026
概括
对Talaromyces radicus的基因组挖掘揭示了具有显著的益血管性和抗炎活性的新型化合物. 删除特定的基因激活了这些化合物,突出了它们的治疗潜力.
科学领域:
- 微生物学 微生物学
- 自然产品化学 自然产品化学
- 分子生物学分子生物学
背景情况:
- 塔拉罗米切斯基根 (Talaromyces radicus) 含有独特的多基酸合成酶 (PKSs).
- 了解真菌中二次代谢物产生的调节对于发现新的生物活性化合物至关重要.
研究的目的:
- 为了研究Talaromyces radicus中异常的非核糖体PKSs (nrPKSs) Tr4942和Tr2381.
- 阐明前体竞争和化合物生产的监管.
- 评估衍生代谢产物的生物活性.
主要方法:
- 基因组挖掘和生物信息学分析以确定nrPKS基因.
- 多种基因组学方法 (基因组学,转录组学,代谢组学) 用于研究基因功能.
- 基因删除和异质表达以验证发现.
- 生物测试以评估亲血管性和抗炎性活动.
主要成果:
- 识别了两个不同的nrPKSs,Tr4942和Tr2381.
- 删除Tr4942导致了9种新的染色体衍生物和4种新的纳夫托基衍生物的激活.
- 鉴定的化合物表现出显著的益血管性和抗炎性质.
- 化合物8通过NF-κB通路调节表现出显著的抗炎作用.
结论:
- 这项研究成功地识别和表征了Talaromyces radicus的新生物活性化合物.
- 这些发现提供了通过前体竞争对二次新陈代谢的调节的见解.
- 发现的染色体和纳夫托基衍生物在炎症和血管生成相关疾病中具有治疗应用的潜力.
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