胆固醇内外 - - 通过其细胞内前体的负反调节
Magdalena Kotowska1, Mateusz Wenecki1, Bartosz Bednarz2
1Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland.
细胞内胆固醇前体 (preCPK) 在Streptomyces coelicolor中抑制胆固醇生物合成. CpkF出口对细胞外CPK生产至关重要,揭示了抗生素监管中的负反循环.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 菌株Streptomyces coelicolor A3(2) 是抗生素生产的一个模型生物.
- 二次代谢物生物合成基因集群 (BGCs) 的调节是复杂的.
- 生物合成产品可以调节调节器的活动.
研究的目的:
- 研究细胞内胆固醇前体 (preCPK) 在调节CPK BGC中的作用.
- 描述集群编码的废流CpkF及其在CPK生产中的作用.
- 确定细胞内或细胞外的CPK化合物是否调节反调节.
主要方法:
- 利用基于 luciferase 的记者系统来比较野生型, ΔcpkF 和 ΔcpkC 菌株中的促进体活性.
- 生成的 ΔcpkF 突变缺少 CPK 出口者.
- 产生了 ΔcpkC 突变,缺乏 CPK 生产.
主要成果:
- 细胞内预CPK参与了负反循环,抑制了CPK BGC.
- CpkF对于细胞外的CPK产生至关重要.
- 在ΔcpkC (没有CPK) 中,促进剂活性上调,在ΔcpkF (没有细胞外CPK) 中类似于WT,表明细胞内CPK沉默了自身的产生.
结论:
- 聚基基基因聚基因作为其自身产生的沉声器,可能通过结合一个未确定的调节蛋白.
- CpkF对于出口CPK至关重要,使细胞外积累和反调节成为可能.
- 这项研究阐明了抗生素生物合成中的新型负反机制.
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