Identification of a gene involved in the synthesis of a dipeptidyl peptidase IV inhibitor in Aspergillus oryzae.
Appl Environ Microbiol
; 78(19): 6996-7002, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22843525
ABSTRACT
WYK-1 is a dipeptidyl peptidase IV inhibitor produced by Aspergillus oryzae strain AO-1. Because WYK-1 is an isoquinoline derivative consisting of three l-amino acids, we hypothesized that a nonribosomal peptide synthetase was involved in its biosynthesis. We identified 28 nonribosomal peptide synthetase genes in the sequenced genome of A. oryzae RIB40. These genes were also identified in AO-1. Among them, AO090001000009 (wykN) was specifically expressed under WYK-1-producing conditions in AO-1. Therefore, we constructed wykN gene disruptants of AO-1 after nonhomologous recombination was suppressed by RNA interference to promote homologous recombination. Our results demonstrated that the disruptants did not produce WYK-1. Furthermore, the expression patterns of 10 genes downstream of wykN were similar to the expression pattern of wykN under several conditions. Additionally, homology searches revealed that some of these genes were predicted to be involved in WYK-1 biosynthesis. Therefore, we propose that wykN and the 10 genes identified in this study constitute the WYK-1 biosynthetic gene cluster.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Sintases
/
Aspergillus oryzae
/
Dipeptidil Peptidase 4
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Inibidores Enzimáticos
/
Isoquinolinas
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Appl Environ Microbiol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Japão