Use of a phosphonate methyltransferase in the identification of the fosfazinomycin biosynthetic gene cluster.
Angew Chem Int Ed Engl
; 53(5): 1334-7, 2014 Jan 27.
Article
em En
| MEDLINE
| ID: mdl-24376039
ABSTRACT
Natural product discovery has been boosted by genome mining approaches, but compound purification is often still challenging. We report an enzymatic strategy for "stable isotope labeling of phosphonates in extract" (SILPE) that facilitates their purification. We used the phosphonate methyltransferase DhpI involved in dehydrophos biosynthesis to methylate a variety of phosphonate natural products in crude spent medium with a mixture of labeled and unlabeled S-adenosyl methionine. Mass-guided fractionation then allowed straightforward purification. We illustrate its utility by purifying a phosphonate that led to the identification of the fosfazinomycin biosynthetic gene cluster. This unusual natural product contains a hydrazide linker between a carboxylic acid and a phosphonic acid. Bioinformatic analysis of the gene cluster provides insights into how such a structure might be assembled.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
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Produtos Biológicos
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Organofosfonatos
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Hidrazinas
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Metiltransferases
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Antibacterianos
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article