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使用合成生物学研究auricin生物合成的初步步骤

Dominika Csolleiova¹, Rachel Javorova¹, Renata Novakova¹

¹Institute of Molecular Biology, Slovak Academy of Sciences, Dubravska Cesta 21, 845 51, Bratislava, Slovak Republic.

|August 8, 2023

概括

这项研究通过描述Streptomyces lavendulae aur1基因集群,揭示了auricin生物合成的关键步骤. 不活跃的合成酶基因被替换,使得拉贝洛米辛的产生成为可能,并突出了aur1和aur2基因集群之间的交叉交谈.

科学领域:

微生物学微生物学
分子生物学分子生物学
合成生物学合成生物学
生物化学生化学

背景情况:

*Streptomyces lavendulae* CCM 3239 具有 *aur1* 基因集群,编码了 II 型多基酸合成酶 (PKS),该基因集群参与了 auricin 生物合成.
奥里的独特的螺旋基质pyranonaphthoquinone aglycone和D-forosamine修饰使其与已知的曲环素区别开来.
了解奥里生物合成的初始步骤对于阐明其新型结构至关重要.

研究的目的:

用合成生物学方法来描述auricin生物合成的最初步骤.
研究生物合成基因 (BGC) *aur1*中的基因的功能.
探索 *aur1* 和相邻的 *aur2* BGC 之间的潜在相互作用.

主要方法:

开发一种合成生物学等离子体系统,利用kasOp*促进体和基于菌体PhiBT1的集成向量.
使用兰多素生物合成基因 (*lanABCFDLE*) 验证该系统,用于在Streptomyces coelicolor* M1146.6中生产拉贝洛素.
通过基因替代和异质表达*aur1* BGC基因的功能分析.

主要成果:

合成系统成功地使用兰多米基因生产了拉贝洛米,验证了等离子体平台的有效性.
在 *aur1* BGC 中,不活跃的合成酶基因 (*aur1DE*) 被确定为rabelomycin生产的瓶.
从*aur2* BGC中用同类基因 (*aur2AB*) 替换 *aur1DE*,恢复并增强了拉贝洛美辛的产生,特别是添加了 *aur1L* (PPTase) 和 *aur1M* (MCAT).

结论:

由*aur1L*编码的4-酸乙烯转移酶 (PPTase) 对于激活乙烯载体蛋白Aur1F至关重要.
这项研究突出了aur1*和aur2*BGCs在auricin aglycone前体的生物合成中的功能交流.
这项工作提供了关于BGC在二次代谢产生的复杂调节和相互作用的见解.

关键词:

抗生素抗生素是一种抗生素.欧里素是一种生物合成基因集群生物合成基因集群灰色的表妹在那里.这种病名为Streptomyces.合成生物学合成生物学

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