Functional analysis of methyltransferases participating in streptothricin-related antibiotic biosynthesis.
J Biosci Bioeng
; 125(2): 148-154, 2018 Feb.
Article
en En
| MEDLINE
| ID: mdl-29029816
ABSTRACT
Streptothricin (ST) and its related compounds produced by Streptomyces strains are broad-spectrum antibiotics that consist of carbamoylated d-gulosamine, amino-acid side chain, and streptolidine lactam moieties. BD-12, a streptothricin-related antibiotic, has a glycine-derived side chain and two N-methyl groups, whereas ST-F carrying the l-ß-lysine side chain has no methyl group. In our previous studies, we identified and characterized the BD-12 and ST biosynthetic gene clusters. Here we report the functional analysis of two methyltransferase genes (orf 6 and orf 13) in the BD-12 biosynthetic gene cluster. Combinatorial biosynthesis using these two methyltransferase genes and the ST biosynthetic gene cluster resulted in the production of three methylated forms of ST-F. Among them, N,N'-dimethyl-ST-F, a novel compound generated in the present study, showed bacteria-specific antibiotic activities, although ST-F exhibits antibiotic activities against both prokaryotes and eukaryotes. Our findings also demonstrated that the orf 6 and orf 13 genes are responsible for the N-methylations of the amide bonds in the streptolidine lactam and in the amino-acid side chain linkage, respectively, and that N-methyl modification of the streptolidine lactam confers resistance in part against an ST hydrolase, SttH.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Streptomyces
/
Estreptotricinas
/
Metiltransferasas
/
Antibacterianos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Biosci Bioeng
Asunto de la revista:
ENGENHARIA BIOMEDICA
/
MICROBIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
JAPAN
/
JAPON
/
JAPÃO
/
JP