Identification and Characterization of the Streptazone E Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08. Issue 16 (25th September 2015)

• Record Type: Journal Article
• Authors: Ohno, Shoto; Katsuyama, Yohei; Tajima, Yuka; Izumikawa, Miho; Takagi, Motoki; Fujie, Manabu; Satoh, Noriyuki; Shin‐ya, Kazuo; Ohnishi, Yasuo
• Is Part Of: Chembiochem. Volume 16:Issue 16(2015)
• Page Start: 2385
• Page End: 2391
• Publication Date: 2015-09-25
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201500317
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Streptazone derivatives isolated from <italic>Streptomyces</italic> species are piperidine alkaloids with a cyclopenta[<italic>b</italic>]pyridine scaffold. Previous studies indicated that these compounds are polyketides, but the biosynthetic enzymes responsible for their synthesis are unknown. Here, we have identified the streptazone E biosynthetic gene cluster in <italic>Streptomyces</italic> sp. MSC090213JE08, which encodes a modular type I PKS and tailoring enzymes that include an aminotransferase, three oxidoreductases, and two putative cyclases. The functions of the six tailoring enzymes were analyzed by gene disruption, and two putative biosynthetic intermediates that accumulated in particular mutants were structurally elucidated. On the basis of these results, we propose a pathway for the biosynthesis of streptazone E in which the two putative cyclases of the nuclear transport factor 2–like superfamily are responsible for C−C bond formation coupled with epoxide ring opening to give the five‐membered ring of streptazone E.</p> </abstract>