Activation and Characterization of Cryptic Gene Cluster: Two Series of Aromatic Polyketides Biosynthesized by Divergent Pathways.
Angew Chem Int Ed Engl
; 58(50): 18046-18054, 2019 12 09.
Article
em En
| MEDLINE
| ID: mdl-31553109
ABSTRACT
One biosynthetic gene cluster (BGC) usually governs the biosynthesis of a series of compounds exhibiting either the same or similar molecular scaffolds. Reported here is a multiplex activation strategy to awaken a cryptic BGC associated with tetracycline polyketides, resulting in the discovery of compounds having different core structures. By constitutively expressing a positive regulator gene in tandem mode, a single BGC directed the biosynthesis of eight aromatic polyketides with two types of frameworks, two pentacyclic isomers and six glycosylated tetracyclines. The proposed biosynthetic pathway, based on systematic gene inactivation and identification of intermediates, employs two sets of tailoring enzymes with a branching point from the same intermediate. These findings not only provide new insights into the role of tailoring enzymes in the diversification of polyketides, but also highlight a reliable strategy for genome mining of natural products.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Streptomyces
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Família Multigênica
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Policetídeos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China