Heterologous Expression of Ilicicolin H Biosynthetic Gene Cluster and Production of a New Potent Antifungal Reagent, Ilicicolin J

Ilicicolin H is a broad-spectrum antifungal agent targeting mitochondrial cytochrome bc1 reductase. Unfortunately, ilicicolin H shows reduced activities in vivo. Here, we report our effort on the identification of ilicicolin H biosynthetic gene cluster (BGC) by genomic sequencing a producing strain,...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-06, Vol.24 (12), p.2267
Main Authors: Lin, Xiaojing, Yuan, Siwen, Chen, Senhua, Chen, Bin, Xu, Hui, Liu, Lan, Li, Huixian, Gao, Zhizeng
Format: Article
Language:English
Subjects:
Biosynthesis
biosynthetic gene cluster
Chemical reactions
Cytochrome
Elongation
Enzymes
Fungicides
Gene clusters
Gene expression
Genes
heterologous production
Homology
ilicicolin H
Intermediates
Metabolites
Methionine
Methyltransferase
Natural products
Neonectria sp. DH2
Peptides
Plasmids
Reagents
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Summary:Ilicicolin H is a broad-spectrum antifungal agent targeting mitochondrial cytochrome bc1 reductase. Unfortunately, ilicicolin H shows reduced activities in vivo. Here, we report our effort on the identification of ilicicolin H biosynthetic gene cluster (BGC) by genomic sequencing a producing strain, sp. DH2, and its heterologous production in . In addition, a shunt product with similar antifungal activities, ilicicolin J, was uncovered. This effort would provide a base for future combinatorial biosynthesis of ilicicolin H analogues. Bioinformatics analysis suggests that the backbone of ilicicolin H is assembled by a polyketide-nonribosomal peptide synthethase (IliA), and then offloaded with a tetramic acid moiety. Similar to tenellin biosynthesis, the tetramic acid is then converted to pyridone by a putative P450, IliC. The decalin portion is most possibly constructed by a -adenosyl-l-methionine (SAM)-dependent Diels-Alderase (IliD).
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24122267