新型真菌二乙生物合成基因集群编码了一种散乱的氧化酶,用于提高抗菌活性
Qingpei Liu1, Shuaibiao Gao1, Jin Fang1
1School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
Chemical science
|August 15, 2024
概括
丝状真菌通过新发现的氧化多酶级联产生二乙烯 (DPE). 这一途径产生DPE类似物,具有针对耐药病原体的广泛抗生素活性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 菌类学 菌类学是指菌类学.
背景情况:
- 双乙烯 (DPE) 是真菌的二次代谢产物.
- 已知的DPE生物合成涉及多基化合成酶 (PKSs) 或Cu氧化酶催化重组.
研究的目的:
- 为了阐明一个新的DPE生物合成途径在*普鲁西亚异构体*.
- 在真菌中识别DPE生产的保存基因集群.
- 为了设计具有抗生素特性的DPE类似物.
主要方法:
- 菌类基因集群的异质表达.
- 对比基因组学以确定保存的生物合成基因.
- 酶工程 (混合氨酶) 改变基质的特异性.
主要成果:
- 发现了第三条DPE生物合成途径,涉及氧化多酶级联转化didepsides为DPEs.
- 在多种真菌物种中发现了这种途径的保存基因集群.
- DpeH 铁酶表现出基质乱交,其C端区域被发现调节基质识别.
- 设计的DPE类似物对抗多药耐药病原体表现出广泛的抗生素活性.
结论:
- 揭示了DPE生物合成的进化保守途径.
- 开发了酶工具来产生新的DPE类似物.
- 这些发现为开发新抗生素来对抗耐药性感染提供了潜力.
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