Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase

Sordarin is a glycoside antibiotic with a unique tetracyclic diterpene aglycone structure called sordaricin. To understand its intriguing biosynthetic pathway that may include a Diels-Alder-type [4+2]cycloaddition, genome mining of the gene cluster from the draft genome sequence of the producer stra...

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Bibliographic Details
Published in:Journal of antibiotics 2016-07, Vol.69 (7), p.541-548
Main Authors: Kudo, Fumitaka, Matsuura, Yasunori, Hayashi, Takaaki, Fukushima, Masayuki, Eguchi, Tadashi
Format: Article
Language:English
Subjects:
631/45/607/1167
631/92/60
82/80
Antifungal Agents - metabolism
Bacteriology
Bioinformatics
Biomedical and Life Sciences
Bioorganic Chemistry
Biosynthesis
Genes, Fungal
Genome, Fungal
Genomics
Glycosyltransferases - genetics
Glycosyltransferases - metabolism
Indenes - metabolism
Life Sciences
Medicinal Chemistry
Microbiology
Organic Chemistry
original-article
Sordariales - enzymology
Sordariales - genetics
Sordariales - metabolism
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Summary:Sordarin is a glycoside antibiotic with a unique tetracyclic diterpene aglycone structure called sordaricin. To understand its intriguing biosynthetic pathway that may include a Diels-Alder-type [4+2]cycloaddition, genome mining of the gene cluster from the draft genome sequence of the producer strain, Sordaria araneosa Cain ATCC 36386, was carried out. A contiguous 67 kb gene cluster consisting of 20 open reading frames encoding a putative diterpene cyclase, a glycosyltransferase, a type I polyketide synthase, and six cytochrome P450 monooxygenases were identified. In vitro enzymatic analysis of the putative diterpene cyclase SdnA showed that it catalyzes the transformation of geranylgeranyl diphosphate to cycloaraneosene, a known biosynthetic intermediate of sordarin. Furthermore, a putative glycosyltransferase SdnJ was found to catalyze the glycosylation of sordaricin in the presence of GDP-6-deoxy- d -altrose to give 4′- O -demethylsordarin. These results suggest that the identified sdn gene cluster is responsible for the biosynthesis of sordarin. Based on the isolated potential biosynthetic intermediates and bioinformatics analysis, a plausible biosynthetic pathway for sordarin is proposed.
ISSN:0021-8820
1881-1469
DOI:10.1038/ja.2016.40