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- Title
Identification of functionally clustered nystatin-like biosynthetic genes in a rare actinomycetes, Pseudonocardia autotrophica.
- Authors
Byung-Gyun Kim; Mi-Jin Lee; Jiyoon Seo; Young-Bin Hwang; Mi-Yeon Lee; Kyuboen Han; Sherman, David H.; Eung-Soo Kim
- Abstract
The polyene antibiotics, including nystatin, pimaricin, amphotericin, and candicidin, comprise a family of very valuable antifungal polyketide compounds, and they are typically produced by soil actinomycetes. Previously, using a polyene cytochrome P450 hydroxylase-specific genome screening strategy, Pseudonocardia autotrophica KCTC9441 was determined to contain genes potentially encoding polyene biosynthesis. Here, sequence information of an approximately 125.7-kb contiguous DNA region in five overlapping cosmids isolated from the P. autotrophica KCTC9441 genomic library revealed a total of 23 open reading frames, which are presumably involved in the biosynthesis of a nystatin-like compound tentatively named NPP. The deduced roles for six multi-modular polyketide synthase (PKS) catalytic domains were found to be highly homologous to those of previously identified nystatin biosynthetic genes. Low NPP productivity suggests that the functionally clustered NPP biosynthetic pathway genes are tightly regulated in P. autotrophica. Disruption of a NPP PKS gene completely abolished both NPP biosynthesis and antifungal activity against Candida albicans, suggesting that polyene-specific genome screening may constitute an efficient method for isolation of potentially valuable previously identified polyene genes and compounds from various rare actinomycetes widespread in nature.
- Subjects
ACTINOBACTERIA; NYSTATIN; ACTINOMYCETALES; GENOMES; CANDIDA albicans; MACROLIDE antibiotics
- Publication
Journal of Industrial Microbiology & Biotechnology, 2009, Vol 36, Issue 11, p1425
- ISSN
1367-5435
- Publication type
Article
- DOI
10.1007/s10295-009-0629-5