Capability of a large bacterial artificial chromosome clone harboring multiple biosynthetic gene clusters for the production of diverse compounds.
J Antibiot (Tokyo)
; 77(5): 288-298, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38438499
ABSTRACT
The biosynthetic gene clusters (BGCs) for the macrocyclic lactone-based polyketide compounds are extremely large-sized because the polyketide synthases that generate the polyketide chains of the basic backbone are of very high molecular weight. In developing a heterologous expression system for the large BGCs amenable to the production of such natural products, we selected concanamycin as an appropriate target. We obtained a bacterial artificial chromosome (BAC) clone with a 211-kb insert harboring the entire BGC responsible for the biosynthesis of concanamycin. Heterologous expression of this clone in a host strain, Streptomyces avermitilis SUKA32, permitted the production of concanamycin, as well as that of two additional aromatic polyketides. Structural elucidation identified these additional products as ent-gephyromycin and a novel compound that was designated JBIR-157. We describe herein sequencing and expression studies performed on these BGCs, demonstrating the utility of large BAC clones for the heterologous expression of cryptic or near-silent loci.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Streptomyces
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Família Multigênica
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Cromossomos Artificiais Bacterianos
Idioma:
En
Revista:
J Antibiot (Tokyo)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão