梅洛克洛林A-D,循环梅洛特类抗生素生物合成在不同的途径与依赖的氧化酶
Leonard Kaysser1, Peter Bernhardt, Sang-Jip Nam
1Scripps Institution of Oceanography, University of California, San Diego, California 92093, USA.
Journal of the American Chemical Society
|July 13, 2012
概括
海洋细菌产生了四种新的penoid抗生素, merochlorins A-D,具有新的结构. 一个依赖的氧化酶基因 (mcl40) 被确定为它们独特生物合成的关键.
科学领域:
- 自然产品化学 自然产品化学
- 海洋微生物学 海洋微生物学
- 生物化学 生物化学
背景情况:
- 梅罗特类是具有多种生物活动的天然产品.
- 海洋微生物是新生物活性化合物的来源.
- Streptomyces 种类是已知的抗生素生产者.
研究的目的:
- 发现和描述一种海洋细菌的新型美罗特类抗生素.
- 为了阐明这些新型化合物的生物合成途径.
- 确定负责关键生物合成步骤的酶.
主要方法:
- 隔离和结构阐明新的美罗特类.
- 生产细菌的基因组测序草案.
- 生物合成基因集群的突变和异质表达.
- 生物化学测试以确定酶功能.
主要成果:
- 确定了四种新的美洛特类物质,美洛克A-D,具有前所未有的化学骨架.
- 鉴定出了一组57.6千亿基因集群,负责梅洛生物合成.
- 在集群中发现了两种依赖的氧化酶 (VHPO) 基因.
- 异质表达表明,Mcl40催化了一种新的诱导的宏循环.
结论:
- 甲基氨酸-甲基氨酸代表了一类新的甲基氨酸抗生素.
- 梅洛生物合成基因集群为自然产品生物合成提供了洞察力.
- VHPO Mcl40催化了一种独特的宏循环化反应,扩大了天然产品合成中已知的酶性转化谱.
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