Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.

Phthoxazolin A, an oxazole-containing polyketide, has a broad spectrum of anti-oomycete activity and herbicidal activity. We recently identified phthoxazolin A as a cryptic metabolite of Streptomyces avermitilis that produces the important anthelmintic agent avermectin. Even though genome data of S....

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Main Authors: Dian Anggraini Suroto, Shigeru Kitani, Masayoshi Arai, Haruo Ikeda, Takuya Nihira
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5764310?pdf=render
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author Dian Anggraini Suroto
Shigeru Kitani
Masayoshi Arai
Haruo Ikeda
Takuya Nihira
author_facet Dian Anggraini Suroto
Shigeru Kitani
Masayoshi Arai
Haruo Ikeda
Takuya Nihira
author_sort Dian Anggraini Suroto
collection DOAJ
description Phthoxazolin A, an oxazole-containing polyketide, has a broad spectrum of anti-oomycete activity and herbicidal activity. We recently identified phthoxazolin A as a cryptic metabolite of Streptomyces avermitilis that produces the important anthelmintic agent avermectin. Even though genome data of S. avermitilis is publicly available, no plausible biosynthetic gene cluster for phthoxazolin A is apparent in the sequence data. Here, we identified and characterized the phthoxazolin A (ptx) biosynthetic gene cluster through genome sequencing, comparative genomic analysis, and gene disruption. Sequence analysis uncovered that the putative ptx biosynthetic genes are laid on an extra genomic region that is not found in the public database, and 8 open reading frames in the extra genomic region could be assigned roles in the biosynthesis of the oxazole ring, triene polyketide and carbamoyl moieties. Disruption of the ptxA gene encoding a discrete acyltransferase resulted in a complete loss of phthoxazolin A production, confirming that the trans-AT type I PKS system is responsible for the phthoxazolin A biosynthesis. Based on the predicted functional domains in the ptx assembly line, we propose the biosynthetic pathway of phthoxazolin A.
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spelling doaj.art-0074bde16a5849838ecf18038825ed0c2022-12-21T18:40:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01131e019097310.1371/journal.pone.0190973Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.Dian Anggraini SurotoShigeru KitaniMasayoshi AraiHaruo IkedaTakuya NihiraPhthoxazolin A, an oxazole-containing polyketide, has a broad spectrum of anti-oomycete activity and herbicidal activity. We recently identified phthoxazolin A as a cryptic metabolite of Streptomyces avermitilis that produces the important anthelmintic agent avermectin. Even though genome data of S. avermitilis is publicly available, no plausible biosynthetic gene cluster for phthoxazolin A is apparent in the sequence data. Here, we identified and characterized the phthoxazolin A (ptx) biosynthetic gene cluster through genome sequencing, comparative genomic analysis, and gene disruption. Sequence analysis uncovered that the putative ptx biosynthetic genes are laid on an extra genomic region that is not found in the public database, and 8 open reading frames in the extra genomic region could be assigned roles in the biosynthesis of the oxazole ring, triene polyketide and carbamoyl moieties. Disruption of the ptxA gene encoding a discrete acyltransferase resulted in a complete loss of phthoxazolin A production, confirming that the trans-AT type I PKS system is responsible for the phthoxazolin A biosynthesis. Based on the predicted functional domains in the ptx assembly line, we propose the biosynthetic pathway of phthoxazolin A.http://europepmc.org/articles/PMC5764310?pdf=render
spellingShingle Dian Anggraini Suroto
Shigeru Kitani
Masayoshi Arai
Haruo Ikeda
Takuya Nihira
Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.
PLoS ONE
title Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.
title_full Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.
title_fullStr Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.
title_full_unstemmed Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.
title_short Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.
title_sort characterization of the biosynthetic gene cluster for cryptic phthoxazolin a in streptomyces avermitilis
url http://europepmc.org/articles/PMC5764310?pdf=render
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AT shigerukitani characterizationofthebiosyntheticgeneclusterforcrypticphthoxazolinainstreptomycesavermitilis
AT masayoshiarai characterizationofthebiosyntheticgeneclusterforcrypticphthoxazolinainstreptomycesavermitilis
AT haruoikeda characterizationofthebiosyntheticgeneclusterforcrypticphthoxazolinainstreptomycesavermitilis
AT takuyanihira characterizationofthebiosyntheticgeneclusterforcrypticphthoxazolinainstreptomycesavermitilis