Biomol Ther  
Streptomyces Cytochrome P450 Enzymes and Their Roles in the Biosynthesis of Macrolide Therapeutic Agents
Myung-A Cho, Songhee Han, Young-Ran Lim, Vitchan Kim, Harim Kim and Donghak Kim,*
Department of Biological Sciences, Konkuk University, Seoul 05025, Republic of Korea
E-mail: donghak@konkuk.ac.krTel: +82-2-450-3366, Fax: +82-2-3436-5432
Received: September 20, 2018; Revised: October 8, 2018; Accepted: October 8, 2018; Published online: December 18, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
The study of the genus Streptomyces is of particular interest because it produces a wide array of clinically important bioactive molecules. The genomic sequencing of many Streptomyces species has revealed unusually large numbers of cytochrome P450 genes, which are involved in the biosynthesis of secondary metabolites. Many macrolide biosynthetic pathways are catalyzed by a series of enzymes in gene clusters including polyketide and non-ribosomal peptide synthesis. In general, Streptomyces P450 enzymes accelerate the final, post-polyketide synthesis steps to enhance the structural architecture of macrolide chemistry. In this review, we discuss the major Streptomyces P450 enzymes research focused on the biosynthetic processing of macrolide therapeutic agents, with an emphasis on their biochemical mechanisms and structural insights.
Keywords: Streptomyces, P450, CYP, Biosynthesis, Macrolide, Secondary metabolite


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