柏金中的乙醇环的生物合成起源
Jeffrey D Rudolf1, Liao-Bin Dong1, Karina Manoogian1
1Department of Chemistry, ‡Department of Molecular Therapeutics, and §Natural Products Library Initiative at The Scripps Research Institute, The Scripps Research Institute , Jupiter, Florida 33458, United States.
研究人员确定了两种关键基因,即ptmT3和ptmO5,这些基因控制了天然产品的不同生物合成途径. 这些发现揭示了PTM的关键结构元素.
科学领域:
- 自然产品生物合成
- 微生物的二次代谢
- 酶催化
背景情况:
- 平坦西米辛 (PTM) 和平坦辛 (PTN) 是一种抑制脂肪酸合成的细菌双胺.
- PTM可以选择性地抑制FabF/FabB,而PTN则可以抑制FabF/FabB和FabH.
- 之前的工作确定了PTM磁带在分离化物生物合成中的作用.
研究的目的:
- 调查PTM磁带在迪特尔化物生物合成分歧中的作用.
- 确定负责PTM和PTN生物合成差异的特定基因.
- 阐明 PtmT3 和 PtmO5 在 PTM/PTN 途径中的功能.
主要方法:
- 在大肠杆菌中构建二烯生产系统.
- 对Streptomyces platensis SB12029 (PTM-PTN双重生产者) 的基因操纵
- 基因失活 (ptmO5) 和累积的PTM/PTN同源的分析.
主要成果:
- 确定了ptmT3和ptmO5作为PTM/PTN生物合成分歧中的关键基因.
- PtmT3是一种新型细菌I型二烯合成酶 (16R) - -16-ol合成酶).
- PtmO5 (细胞染色体P450) 可能形成PTM环;其无活化产生了新型同源物.
结论:
- PTM 磁带,特别是 PtmT3 和 PtmO5,决定了 PTM 和 PTN 化物的分离生物合成.
- 11S,16S-环或C-16立体化学对于PTM的抗菌活性至关重要.
- 发现一种新的细菌二烯合成酶,并深入了解PTM/PTN生物合成和结构-活性关系.
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