糖酸的cis-Delta(2,3) 双键是由一个后PKS定制酶生成的
Nadaraj Palaniappan1, Mamoun M Alhamadsheh, Kevin A Reynolds
1Department of Chemistry, Portland State University, Portland, OR 97297, USA.
Journal of the American Chemical Society
|August 22, 2008
概括
抗真菌菌素 (PLM) 具有不寻常的cis双键. 一个新的基因,plmT2,对于形成cis Delta2,3基是必不可少的,揭示了对多基基生物合成的新见解.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 自然产品生物合成 自然产品生物合成
背景情况:
- 菌素 (PLM) 是一种具有独特 cis 双键的抗真菌化合物.
- 多基化合成酶 (PKS) 途径通常使用脱水酶域来形成双键.
- 由于没有预测的PKS脱水酶域,PLM中cis Delta2,3双键的形成是无法解释的.
研究的目的:
- 为了阐明黄菌素中cis Delta2,3双键的形成背后的机制.
- 为了确定对这种不寻常的生物合成步骤负责的遗传因素.
- 为了了解马洛尼化聚基化物产品的生成.
主要方法:
- 在Streptomyces sp.中,plmT2的基因缺失突变发生. 港币803.3元. 这是一个很好的选择.
- 使用分析化学技术分析突变菌株的PLM产品.
- 补充研究涉及plmT2和fos ORF4.4基于等离子体的表达.
- 对基质催化脱碳氧化消除反应的研究.
主要成果:
- plmT2基因产物缺乏PKS脱水酶域的同质性,对高效的cis Delta2,3基因形成至关重要.
- plmT2删除突变产生了保留C3基组的PLM变异,这些变异是有恶的.
- 这些恶化中间体通过基质催化脱氧化消除转化为cis Delta2,3 PLMs.
- 在删除突变体中,plmT2或fos ORF4的表达恢复了自然PLM生产.
结论:
- 脱水酶独立路径可以在PKS路径的不和乳部分中建立cis双键.
- plmT2基因产物代表了多基化生物合成中的新型因子.
- 这项研究提供了第一个生物合成洞察力,以了解不同寻常的恶聚化物产品的形成.
- 这些发现扩大了我们对多基化天然产品生物合成中的多样性和机制的理解.
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