Liu Xiangyang
UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Synth Syst Biotechnol. 2016 Feb 26;1(2):95-108. doi: 10.1016/j.synbio.2016.01.007. eCollection 2016 Jun.
The increased number of annotated bacterial genomes provides a vast resource for genome mining. Several bacterial natural products with epoxide groups have been identified as pre-mRNA spliceosome inhibitors and antitumor compounds through genome mining. These epoxide-containing natural products feature a common biosynthetic characteristic that cytochrome P450s (CYPs) and its patterns such as epoxidases are employed in the tailoring reactions. The tailoring enzyme patterns are essential to both biological activities and structural diversity of natural products, and can be used for enzyme pattern-based genome mining. Recent development of direct cloning, heterologous expression, manipulation of the biosynthetic pathways and the CRISPR-CAS9 system have provided molecular biology tools to turn on or pull out nascent biosynthetic gene clusters to generate a microbial natural product library. This review focuses on a library of epoxide-containing natural products and their associated CYPs, with the intention to provide strategies on diversifying the structures of CYP-catalyzed bioactive natural products. It is conceivable that a library of diversified bioactive natural products will be created by pattern-based genome mining, direct cloning and heterologous expression as well as the genomic manipulation.
注释细菌基因组数量的增加为基因组挖掘提供了丰富的资源。通过基因组挖掘，已鉴定出几种带有环氧基团的细菌天然产物作为前体信使核糖核酸剪接体抑制剂和抗肿瘤化合物。这些含环氧基团的天然产物具有共同的生物合成特征，即细胞色素P450（CYPs）及其诸如环氧化酶等模式被用于修饰反应。修饰酶模式对于天然产物的生物活性和结构多样性都至关重要，并且可用于基于酶模式的基因组挖掘。直接克隆、异源表达、生物合成途径的操纵以及CRISPR-CAS9系统的最新发展提供了分子生物学工具，以开启或挖掘新生的生物合成基因簇，从而生成微生物天然产物文库。本综述聚焦于含环氧基团天然产物及其相关CYPs的文库，旨在提供使CYP催化的生物活性天然产物结构多样化的策略。可以想象，通过基于模式的基因组挖掘、直接克隆和异源表达以及基因组操作，将创建一个多样化的生物活性天然产物文库。
