Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1

K. Qiao, Heng Chooi, Y. Tang

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a producer of cytochalasin E and K, the genome of A. clavatus was analyzed and the ~30 kb ccs gene cluster was identified based on the presence of a polyketide synthase-nonribosomal peptide synthetases (PKS-NRPS) and a putative Baeyer-Villiger monooxygenase (BVMO). Deletion of the central PKS-NRPS gene, ccsA, abolished the production of cytochalasin E and K, confirming the association between the natural products and the gene cluster. Based on bioinformatic analysis, a putative biosynthetic pathway is proposed. Furthermore, overexpression of the pathway specific regulator ccsR elevated the titer of cytochalasin E from 25 mg/L to 175 mg/L. Our results not only shed light on the biosynthesis of cytochalasins, but also provided genetic tools for increasing and engineering the production. © 2011 Elsevier Inc..
Original languageEnglish
Pages (from-to)723-732
JournalMetabolic Engineering
Volume13
Issue number6
DOIs
Publication statusPublished - 2011

Fingerprint

Cytochalasins
Aspergillus
Multigene Family
Genes
Peptide Synthases
Polyketide Synthases
Peptides
Biosynthetic Pathways
Mixed Function Oxygenases
Computational Biology
Biological Products
Biosynthesis
Bioinformatics
Metabolites
Bioactivity
Genome
cytochalasin E
Association reactions

Cite this

@article{edfd9f5188904173808d7212379efa47,
title = "Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1",
abstract = "Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a producer of cytochalasin E and K, the genome of A. clavatus was analyzed and the ~30 kb ccs gene cluster was identified based on the presence of a polyketide synthase-nonribosomal peptide synthetases (PKS-NRPS) and a putative Baeyer-Villiger monooxygenase (BVMO). Deletion of the central PKS-NRPS gene, ccsA, abolished the production of cytochalasin E and K, confirming the association between the natural products and the gene cluster. Based on bioinformatic analysis, a putative biosynthetic pathway is proposed. Furthermore, overexpression of the pathway specific regulator ccsR elevated the titer of cytochalasin E from 25 mg/L to 175 mg/L. Our results not only shed light on the biosynthesis of cytochalasins, but also provided genetic tools for increasing and engineering the production. {\circledC} 2011 Elsevier Inc..",
author = "K. Qiao and Heng Chooi and Y. Tang",
year = "2011",
doi = "10.1016/j.ymben.2011.09.008",
language = "English",
volume = "13",
pages = "723--732",
journal = "Metabolic Engineering",
issn = "1096-7176",
publisher = "Academic Press",
number = "6",

}

Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1. / Qiao, K.; Chooi, Heng; Tang, Y.

In: Metabolic Engineering, Vol. 13, No. 6, 2011, p. 723-732.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1

AU - Qiao, K.

AU - Chooi, Heng

AU - Tang, Y.

PY - 2011

Y1 - 2011

N2 - Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a producer of cytochalasin E and K, the genome of A. clavatus was analyzed and the ~30 kb ccs gene cluster was identified based on the presence of a polyketide synthase-nonribosomal peptide synthetases (PKS-NRPS) and a putative Baeyer-Villiger monooxygenase (BVMO). Deletion of the central PKS-NRPS gene, ccsA, abolished the production of cytochalasin E and K, confirming the association between the natural products and the gene cluster. Based on bioinformatic analysis, a putative biosynthetic pathway is proposed. Furthermore, overexpression of the pathway specific regulator ccsR elevated the titer of cytochalasin E from 25 mg/L to 175 mg/L. Our results not only shed light on the biosynthesis of cytochalasins, but also provided genetic tools for increasing and engineering the production. © 2011 Elsevier Inc..

AB - Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a producer of cytochalasin E and K, the genome of A. clavatus was analyzed and the ~30 kb ccs gene cluster was identified based on the presence of a polyketide synthase-nonribosomal peptide synthetases (PKS-NRPS) and a putative Baeyer-Villiger monooxygenase (BVMO). Deletion of the central PKS-NRPS gene, ccsA, abolished the production of cytochalasin E and K, confirming the association between the natural products and the gene cluster. Based on bioinformatic analysis, a putative biosynthetic pathway is proposed. Furthermore, overexpression of the pathway specific regulator ccsR elevated the titer of cytochalasin E from 25 mg/L to 175 mg/L. Our results not only shed light on the biosynthesis of cytochalasins, but also provided genetic tools for increasing and engineering the production. © 2011 Elsevier Inc..

U2 - 10.1016/j.ymben.2011.09.008

DO - 10.1016/j.ymben.2011.09.008

M3 - Article

VL - 13

SP - 723

EP - 732

JO - Metabolic Engineering

JF - Metabolic Engineering

SN - 1096-7176

IS - 6

ER -