循环自然产品的寡合体:宏观循环的多样性和 (生物) 合成
Songya Zhang1,2, Shuai Fan3, Haocheng He1,2
1CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Chemical Society reviews
|November 25, 2024
概括
循环化合物在药物开发中具有优势. 本综述强调了硫酶 (TE) 域和其他催化剂,用于合成环二烯天然产品,增强化学多样性和生物活性.
科学领域:
- 生物化学和天然产品合成
- 酵素学和生物催化剂学
背景情况:
- 循环化合物在功能研究中是首选的,因为与线性类似物相比,它们的生物可用性,代谢稳定性和受体结合性优越.
- 硫酶 (TE) 域是天然产品生物合成中的关键生物催化剂,增强循环分子的化学多样性和生物活性.
- 宏循环,特别是通过非核糖体合成酶 (NRPS) 和多基合成酶 (PKS) 路径形成循环二元天然产物,带来了重大的生物合成挑战.
研究的目的:
- 审查涉及生物合成和化学合成中的宏循环化自然产品.
- 突出 TE 域的功能和生物合成研究,这些 TE 域负责循环合物天然产品的形成.
- 引入其他宏循环化催化剂,激发新型生物活性分子的发现.
主要方法:
- 对自然产品生物合成和化学合成中的宏循环化策略现有文献的审查.
- 专注于参与循环二烯化合物形成的铁酶 (TE) 域的表征和功能.
- 探索替代的宏循环化催化剂,如布氏酶,CT介导的循环化和循环二合成酶 (CDPS).
主要成果:
- TE域是宏循环化的关键生物催化剂,特别是在NRPS和PKS路径中形成循环体的自然产物中.
- 虽然TE域的表征已经得到了进展,但专门形成环二烯化合物的酶仍然难以捉摸.
- 其他催化剂,如布氏酶,CT介导循环和CDPS也介导宏循环,扩大了循环化合物合成的工具包.
结论:
- 对于合成化学和药物发现至关重要的是了解循环二天然产品的生物合成.
- 需要对 TE 领域和其他宏循环化催化剂进行进一步的研究,以释放它们的全部潜力.
- 本综述为合成化学家,药物发现小组和酶学家提供了宝贵的见解,促进了生物活性分子开发方面的创新.
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