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Biosynthesis and pathway engineering of antifungal polyene macrolides in actinomycetes

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Journal of Industrial Microbiology & Biotechnology

Abstract

Polyene macrolides are a large family of natural products typically produced by soil actinomycetes. Polyene macrolides are usually biosynthesized by modular and large type I polyketide synthases (PKSs), followed by several steps of sequential post-PKS modifications such as region-specific oxidations and glycosylations. Although known as powerful antibiotics containing potent antifungal activities (along with additional activities against parasites, enveloped viruses and prion diseases), their high toxicity toward mammalian cells and poor distribution in tissues have led to the continuous identification and structural modification of polyene macrolides to expand their general uses. Advances in in-depth investigations of the biosynthetic mechanism of polyene macrolides and the genetic manipulations of the polyene biosynthetic pathways provide great opportunities to generate new analogues. Recently, a novel class of polyene antibiotics was discovered (a disaccharide-containing NPP) that displays better pharmacological properties such as improved water-solubility and reduced hemolysis. In this review, we summarize the recent advances in the biosynthesis, pathway engineering, and regulation of polyene antibiotics in actinomycetes.

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Acknowledgments

This work was supported by a grant from the Next-Generation BioGreen 21 Program, Rural Development Administration (RDA), and also in part by the 21C Frontier Microbial Genomics and Applications Center Program [11-2008-15-003-00] from the National Research Foundation (NRF) of Korea.

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Correspondence to Shuangjun Lin or Eung-Soo Kim.

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Dekun Kong and Mi-Jin Lee contributed equally to this work.

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Kong, D., Lee, MJ., Lin, S. et al. Biosynthesis and pathway engineering of antifungal polyene macrolides in actinomycetes. J Ind Microbiol Biotechnol 40, 529–543 (2013). https://doi.org/10.1007/s10295-013-1258-6

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