工程生物用于脱氧糖生物合成和产生新的四烯菌素
Heli Tirkkonen1, Katelyn V Brown2, Magdalena Niemczura1
1Department of Life Technologies, University of Turku, FIN-20014 Turku, Finland.
ACS omega
|June 19, 2023
概括
研究人员使用BioBricks在Streptomyces中设计了脱氧糖生物合成. 这使得能够创造出具有多种糖修饰的新型四诺米辛化合物,扩大了天然产品的多样性.
科学领域:
- 自然产品生物合成 自然产品生物合成
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
背景情况:
- 烯胺和埃洛拉胺是来自actinomycete的多基胺,具有抗菌和抗癌特性.
- 这些化合物通过与大型核糖体子单元的多退出通道结合来抑制核糖体翻译.
- 这些天然产品的结构差异,包括O-甲基化和特定的糖附着物,如2',3',4'-tri-O-methyl-α-l-rhamnose在埃洛拉米中,区分这些天然产品.
研究的目的:
- 开发BioBricks基因磁带,用于在Streptomyces物种中设计脱氧糖生物合成途径.
- 为了利用BioBricks表达平台来进行四烯胺化合物的糖多样化.
- 为了产生具有多种脱氧糖修饰的新型氏胺衍生物.
主要方法:
- 开发用于脱氧糖生物合成的BioBricks基因盒.
- 链状菌的代谢工程 coelicolor M1146::cos16F4iE,一个宿主工程为8-demethyl-tetracenomycin C生产和ElmGT表达.
- 使用乱交的糖系转移酶ElmGT转移各种TDP-脱氧糖基质.
主要成果:
- 成功设计了d配置的TDP-脱氧糖的生物合成,产生已知的化合物,如8-O-d-glucosyl-tetracenomycin C.
- 产生了四种新的四氧化衍生物:8-O-4'-keto-d-digitoxosyl-tetracenomycin C,8-O-d-fucosyl-tetracenomycin C,8-O-d-allosyl-tetracenomycin C,以及8-O-d-quinovosyl-tetracenomycin C. 这四种新衍生物包括:8-O-4'-keto-d-digitoxosyl-tetracenomycin C,8-O-d-fucosyl-tetracenomycin C,8-O-d-allosyl-tetracenomycin C,以及8-O-d-quinovosyl-tetracenomycin C. 这四种新衍生物包括:
- 证明了BioBricks克隆的可行性,用于快速组装碳水化合物通路和糖分多样化.
结论:
- 克隆BioBricks是一种有效的策略,用于组装不同的碳水化合物通路.
- 这种方法使得天然产品如四诺素的快速糖分多样化成为可能.
- 开发的方法有助于产生具有潜在治疗应用的新生物活性化合物.
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