Generate a bioactive natural product library by mining bacterial cytochrome P450 patterns

Area of Science:

• Natural Product Chemistry
• Genomics
• Biotechnology

Background:

• Annotated bacterial genomes offer extensive resources for discovering novel compounds.
• Bacterial natural products containing epoxide groups exhibit significant pre-mRNA spliceosome inhibitory and antitumor activities.
• Cytochrome P450s (CYPs) and their epoxidase patterns are crucial for the biosynthesis and structural diversity of these bioactive natural products.

Purpose of the Study:

• To review epoxide-containing natural products and their associated CYPs.
• To propose strategies for diversifying CYP-catalyzed bioactive natural products.
• To highlight the potential of enzyme pattern-based genome mining for natural product discovery.

Main Methods:

• Genome mining of bacterial genomes.
• Analysis of cytochrome P450 (CYP) enzyme patterns in natural product biosynthesis.
• Leveraging molecular biology tools including direct cloning, heterologous expression, and CRISPR-CAS9 systems.
• Generating microbial natural product libraries through biosynthetic pathway manipulation.

Main Results:

• Identification of several bacterial natural products with epoxide groups possessing biological activities.
• Elucidation of the role of CYPs and epoxidases in tailoring reactions for structural diversity.
• Demonstration of molecular tools for activating or retrieving silent biosynthetic gene clusters.

Conclusions:

• Enzyme pattern-based genome mining, coupled with advanced molecular tools, can generate diverse libraries of bioactive natural products.
• Diversification of CYP-catalyzed natural products is achievable through strategic manipulation of biosynthetic pathways.
• This approach holds promise for the discovery of novel therapeutic agents.