通过Streptomyces coelicolor基因组挖掘发现的III型聚基酸合成酶β-ketoacyl-ACP启动单元和乙基烯-CoA扩展单元的选择性
Lijiang Song1, Francisco Barona-Gomez, Christophe Corre
1Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K
Journal of the American Chemical Society
|November 16, 2006
概括
这项研究表明,来自Streptomyces coelicolor的III型多基化合成酶 (PKS) Gcs可以合成细菌素. 格斯独特地使用脂肪酸合成酶产品作为起始单元和乙基-CoA作为扩展单元.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 自然产品的合成自然产品的合成
背景情况:
- 聚基化合成酶 (PKSs) 是自然产品生物合成中的关键酶.
- 细菌中的III型PKS通常通过malonyl-CoA凝结产生多氧芳香化合物.
- 细菌Streptomyces coelicolor是众所周知的各种二次代谢物的生产者.
研究的目的:
- 为了研究Streptomyces coelicolor中III型PKS Gcs (编码为sco7221) 的功能.
- 为了阐明germicidin天然产品家族的生物合成途径.
- 在自然产品组装中描述Gcs的基质特异性.
主要方法:
- 在Streptomyces coelicolor.中Gcs基因 (sco7221) 的基因淘汰/破坏.
- 分析聚基酸合成酶活性和产品识别.
- 生物化学试验以确定Gcs.的基质利用率.
主要成果:
- Gcs对于生菌素的生物合成至关重要,这是3,6-二甲基-4-基-2-one天然产品的家族.
- 有证据表明,Gcs通过乙基-CoA或甲基-CoA延长β-基-ACP起始单元 (来自脂肪酸合成酶FabH).
- 作为扩展剂,Gcs对β-ketoacyl-ACP启动剂和乙烯基醇-CoA具有前所未有的选择性.
结论:
- Gcs在细菌素生物合成中发挥着特定的作用.
- 第三种类型的PKS具有比以前更广泛的基板范围,利用不同的启动和扩展单元.
- 这一发现扩大了我们对自然产品多样性的酶机制的理解.
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