Chemical induction of silent biosynthetic pathway transcription in Aspergillus niger.
J Ind Microbiol Biotechnol
; 36(9): 1199-213, 2009 Sep.
Article
em En
| MEDLINE
| ID: mdl-19521728
ABSTRACT
Manipulation of the fungal epigenome is hypothesized to be an effective method for accessing natural products from silent biosynthetic pathways. A library of epigenetic modifiers was tested using the fungus Aspergillus niger to determine the impact of small-molecule inhibitors on reversing the transcriptional suppression of biosynthetic genes involved in polyketide (PKS), non-ribosomal peptide (NRPS), and hybrid PKS-NRPS (HPN) production. Examination of expressed sequence tag libraries from A. niger demonstrated that >70% of its PKS-, NRPS-, and HPN-encoding gene clusters were transcriptionally suppressed under standard laboratory culture conditions. Using a chemical epigenetic methodology, we showed that treatment of A. niger with suberoylanilide hydroxamic acid and 5-azacytidine led to the transcriptional upregulation of many secondary-metabolite-encoding biosynthetic gene clusters. Chemical epigenetic modifiers exhibited positional biases for upregulating chromosomally distal gene clusters. In addition, a phylogenetic-based preference was noted in the upregulation of reducing clade I PKS gene clusters, while reducing clade IV PKS gene clusters were largely unaffected. Manipulating epigenetic features in fungi is a powerful method for accessing the products of silent biosynthetic pathways. Moreover, this approach can be readily incorporated into modern microbial screening operations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aspergillus niger
/
Azacitidina
/
Biotecnologia
/
Proteínas Fúngicas
/
Regulação Fúngica da Expressão Gênica
/
Família Multigênica
/
Vias Biossintéticas
/
Ácidos Hidroxâmicos
Tipo de estudo:
Evaluation_studies
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article