Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function

Area of Science:

• Biochemistry and Molecular Biology
• Natural Product Chemistry
• Microbial Biotechnology

Background:

• Cytochrome P450 enzymes (P450s) are crucial metalloenzymes involved in diverse biological processes, including drug metabolism and natural product biosynthesis.
• The Streptomyces genus is a prolific source of natural products, necessitating a deep understanding of its associated P450 enzymes.
• Despite their importance, a vast majority of P450s in Streptomyces remain functionally and structurally uncharacterized.

Purpose of the Study:

• To review and summarize the functionally characterized Cytochrome P450 enzymes within the Streptomyces genus.
• To explore the sequence-function relationships of P450s using a large-scale sequence similarity network.
• To highlight the established and potential applications of Streptomyces P450s in biomedical and biotechnological fields.

Main Methods:

• Bioinformatic analysis of a sequence similarity network comprising over 8500 P450 sequences from Streptomyces.
• Comprehensive literature survey and summarization of functionally characterized P450s from Streptomyces.
• Analysis of existing data to infer sequence-function relationships and catalytic capabilities.

Main Results:

• The study surveyed the catalytic landscape of P450s in Streptomyces, identifying key enzymes involved in natural product biosynthesis.
• A sequence similarity network revealed insights into the sequence-function relationships of these oxygen-dependent enzymes.
• Only a small fraction (<2.4%) of Streptomyces P450s have been functionally characterized, indicating significant unexplored potential.

Conclusions:

• Streptomyces P450s exhibit diverse roles in natural product biosynthesis, expanding the known catalytic repertoire of these enzymes.
• Characterized P450s have established structural and mechanistic paradigms, demonstrating potential for biomedical and biotechnological applications.
• Further investigation into Streptomyces P450s is essential to fully realize their chemical and biological capabilities.