Polyene antibiotic biosynthesis gene clusters

Over the past 15 years the biosynthetic gene clusters for numerous bioactive polyketides have been intensively studied and recently this work has been extended to the antifungal polyene macrolides. These compounds consist of large macrolactone rings that have a characteristic series of conjugated do...

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Bibliographic Details
Published in:Applied microbiology and biotechnology 2003-05, Vol.61 (3), p.179-188
Main Authors: APARICIO, J. F, CAFFREY, P, GIL, J. A, ZOTCHEV, S. B
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - biosynthesis
Anti-Bacterial Agents - chemistry
Antibiotics
Antifungal agents
Bacteria - genetics
Bacteria - metabolism
Biological and medical sciences
Biosynthesis
Cytochrome
Evolution, Molecular
Fundamental and applied biological sciences. Psychology
Genes
Genetic aspects
Genetic Engineering
Genetics
Multigene Family - genetics
Physiological aspects
Polyenes - chemistry
Polyenes - metabolism
Proteins
Studies
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Summary:Over the past 15 years the biosynthetic gene clusters for numerous bioactive polyketides have been intensively studied and recently this work has been extended to the antifungal polyene macrolides. These compounds consist of large macrolactone rings that have a characteristic series of conjugated double bonds, as well as an exocyclic carboxyl group and an unusual mycosamine sugar. The biosynthetic gene clusters for nystatin, pimaricin, amphotericin and candicidin have been investigated in detail. These clusters contain the largest modular polyketide synthase genes reported to date. This body of work also provides insights into the enzymes catalysing the unusual post-polyketide modifications, and the genes regulating antibiotic biosynthesis. The sequences also provide clues about the evolutionary origins of polyene biosynthetic genes. Successful genetic manipulation of the producing organisms leading to production of polyene analogues indicates good prospects for generating improved antifungal compounds via genetic engineering.
ISSN:0175-7598
1432-0614
DOI:10.1007/s00253-002-1183-5