发现了一种新的单一功能分子间迪尔斯-阿尔德酶,用于 hetero-dimer lithocarpins 的生物合成
Wei Ye1, Shan Liu1, Xinna Yang1
1State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Institute of Microbiology, Guangdong Academy of Sciences, No. 100 Xianlie Middle Road, Yuexiu District, Guangzhou 510070, China.
研究人员发现了一种新的Diels-Alder (DA) 酶,g7882,对于在深海真菌Phomopsis lithocarpus中产生抗瘤石墨素至关重要. 这种酶和其他遗传因素是理解和增强这些有价值化合物的生物合成的关键.
科学领域:
- 海洋天然产品化学 海洋天然产品化学
- 菌类生物化学 菌类生物化学
- 酶学 是一种酶学.
背景情况:
- 深海真菌 Phomopsis lithocarpus FS508 产生石墨烯 A-G,强大的抗瘤剂.
- 对分子间迪尔斯-阿尔德 (DA) 酶的有限理解阻碍了新生物活性异构体的发现.
研究的目的:
- 为了识别和描述参与石化生物合成的新型酶.
- 为了阐明 hetero-dimer lithocarpins 的生物合成途径.
- 探索这些酶生产新生物活性化合物的潜力.
主要方法:
- 在P. lithocarpus FS508.8.中的基因淘汰和候选基因过度表达.
- 生物化学测试以证实酶功能在体外.
- 使用基因操纵对二次代谢物产生的分析.
主要成果:
- 一个新的单一功能分子间DA酶,g7882,被确定并证实是 lithocarpin A 生产必不可少的.
- 删除g7882取消了Lithocarpin A,而它的过度表达增加了产量.
- 在PKS集群41和81中的KS模块的淘汰消除了石化,证实了DA酶在它们的生物合成中的作用.
- 对GPAT和prenyltransferase基因的操纵影响了 lithocarpin A水平,GPAT过度表达产生了一种新衍生物,Lithocarol G.
结论:
- g7882 是一种关键酶,通过分子间DA反应合成 hetero-dimer lithocarpins.
- 这项研究为 lithocarpins 的生物合成逻辑提供了关键的见解.
- 鉴定到的DA酶为新型异构二次体的生物合成提供了一个新的工具,具有潜在的治疗应用.
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