• 特约评述 •
程中玉, 李付琸
收稿日期:
2024-02-04
修回日期:
2024-05-21
出版日期:
2024-06-11
通讯作者:
李付琸
作者简介:
基金资助:
Zhongyu CHENG, Fuzhuo LI
Received:
2024-02-04
Revised:
2024-05-21
Online:
2024-06-11
Contact:
Fuzhuo LI
摘要:
随着基因挖掘、生物信息学、酶工程等多学科的交叉融合与协同创新,将绿色高效的酶催化反应与现代有机合成方法相结合的化学-酶法合成策略逐渐发展成为合成活性天然产物、药物分子和其它具有重要价值的有机分子的有力工具。其中细胞色素单加氧酶P450能够选择性地实现惰性C-H氧化这一经典的挑战性化学转化,为活性天然产物的高效合成提供了新的思路,成为合成科学领域的研究热点之一。本文以结构类型进行分类,综述了P450选择性氧化在甾体、萜类以及其他类型天然产物化学-酶法合成中的应用进展,并分析了相应的酶催化反应在提高目标产物合成效率方面起到的关键作用。此外,本文还讨论了该领域目前所面临的挑战,例如主要集中在对酶天然功能的利用,并缺乏对反应位点的准确预测等;同时从酶资源挖掘、酶的改造等多个角度出发展望了未来能够为这些挑战提供解决方案的研究方向和新兴技术,包括高通量筛选技术、AI辅助酶工程等等。
中图分类号:
程中玉, 李付琸. 基于P450选择性氧化的天然产物化学-酶法合成进展[J]. 合成生物学, DOI: 10.12211/2096-8280.2024-017.
Zhongyu CHENG, Fuzhuo LI. Recent advances in chemoenzymatic synthesis of natural products via site- selective P450 oxidation[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2024-017.
图3 (a) CYP11411和CYP44476的区域选择性;(b) bufotalin、bufogenin和digitoxigenin的化学-酶法合成
Fig. 3 (a) Regioselectivity of CYP11411and CYP44476;(b) Chemoenzymatic synthesis of bufotalin, bufogenin and digitoxigenin
图4 (a) Regioselectivity of CYP14A I111L-V124W;(b)野生型CYP14A和突变体的对比;(c)Digitoxigenin、3α-hydroxyldigitoxigenin和periplogenin的化学-酶法合成
Fig. 4 (a) Regioselectivity of CYP14A I111L-V124W; (b) Comparison of the wide-type CYP14A and mutant; (c) Chemoenzymatic synthesis of digitoxigenin, 3α-hydroxyldigitoxigenin and periplogenin.
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