Publication: Activation of cryptic milbemycin A<inf>4</inf> production in Streptomyces sp. BB47 by the introduction of a functional bldA gene
Issued Date
2021-01-01
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ISSN
13498037
00221260
00221260
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2-s2.0-85123389170
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of General and Applied Microbiology. Vol.67, No.6 (2021), 240-247
Suggested Citation
Nana Matsui, Shizuka Kawakami, Dai Hamamoto, Sayuri Nohara, Reina Sunada, Watanalai Panbangred, Yasuhiro Igarashi, Takuya Nihira, Shigeru Kitani Activation of cryptic milbemycin A<inf>4</inf> production in Streptomyces sp. BB47 by the introduction of a functional bldA gene. Journal of General and Applied Microbiology. Vol.67, No.6 (2021), 240-247. doi:10.2323/jgam.2021.04.001 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/77336
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Title
Activation of cryptic milbemycin A<inf>4</inf> production in Streptomyces sp. BB47 by the introduction of a functional bldA gene
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Abstract
Streptomycetes are characterized by their ability to produce structurally diverse compounds as secondary metabolites and by their complex developmental life cycle, which includes aerial mycelium formation and sporulation. The production of secondary metabolites is growth-stage dependent, and generally coincides with morphological development on a solid culture. Streptomyces sp. BB47 pro-duces several types of bioactive compounds and displays a bald phenotype that is devoid of an aerial mycelium and spores. Here, we demonstrated by genome analysis and gene complementation experi-ments that the bald phenotype arises from the bldA gene, which is predicted to encode the Leu-tRNAUUA molecule. Unlike the wild-type strain producing jomthonic acid A (1) and antarlide A (2), the strain complemented with a functional bldA gene newly produced milbemycin (3). The chemical structure of compound 3 was elucidated on the basis of various spectroscopic analyses, and was identified as milbemycin A4, which is an insecti-cidal/acaricidal antibiotic. These results indicate that genetic manipulation of genes involved in morphological development in streptomycetes is a valu-able way to activate cryptic biosynthetic pathways.