Work

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

Year: 2017

Type: review

Abstract: Covering: up to January 2017Cytochrome P450 enzymes (P450s) are some of the most exquisite and versatile biocatalysts found in nature. In addition to their well-known roles in steroid biosynthesis and drug metabolism in humans, P450s are key players in natural product biosynthetic pathways. Natural products, the most chemically and structurally diverse small molecules known, require an extensive collection of P450s to accept and functionalize their unique scaffolds. In this review, we survey the current catalytic landscape of P450s within the Streptomyces genus, one of the most prolific producers of natural products, and comprehensively summarize the functionally characterized P450s from Streptomyces. A sequence similarity network of >8500 P450s revealed insights into the sequence-function relationships of these oxygen-dependent metalloenzymes. Although only ∼2.4% and <0.4% of streptomycete P450s have been functionally and structurally characterized, respectively, the study of streptomycete P450s involved in the biosynthesis of natural products has revealed their diverse roles in nature, expanded their catalytic repertoire, created structural and mechanistic paradigms, and exposed their potential for biomedical and biotechnological applications. Continued study of these remarkable enzymes will undoubtedly expose their true complement of chemical and biological capabilities.

Source: Natural Product Reports

DOI: 10.1039/c7np00034k

Authors: Jeffrey D. Rudolf, Chin-Yuan Chang, Ming Ma, Ben Shen

Institutions: Scripps Research Institute, Jupiter (United States)

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology (medical)

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences