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Identification of functionally clustered nystatin-like biosynthetic genes in a rare actinomycetes, Pseudonocardia autotrophica

  • Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

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.

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Acknowledgments

The authors appreciate Professor Sergey B. Zochev at Norwegian University of Science and Technology who kindly provided the authentic nystatin sample as well as some critical comments. This work was financially supported by a 21C Frontier R&D program grant from the Korean Ministry of Education, Science and Technology, and also NIH grant GM076477 to DHS.

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Authors and Affiliations

  1. Department of Biological Engineering, Inha University, Incheon, 402-751, Korea

    Byung-Gyun Kim, Mi-Jin Lee, Jiyoon Seo, Young-Bin Hwang, Mi-Yeon Lee & Eung-Soo Kim

  2. Hanson Biotech Co., Ltd. 201 IACRI, Han Nam University, Daejeon, 306-791, Korea

    Kyuboen Han

  3. Life Sciences Institute and Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, 48109-2216, USA

    David H. Sherman

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  1. Byung-Gyun Kim
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Correspondence to Eung-Soo Kim.

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B. G. Kim and M. J. Lee contributed equally.

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Kim, BG., Lee, MJ., Seo, J. et al. Identification of functionally clustered nystatin-like biosynthetic genes in a rare actinomycetes, Pseudonocardia autotrophica . J Ind Microbiol Biotechnol 36, 1425–1434 (2009). https://doi.org/10.1007/s10295-009-0629-5

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  • DOI: https://doi.org/10.1007/s10295-009-0629-5

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