Nana MatsuiShizuka KawakamiDai HamamotoSayuri NoharaReina SunadaWatanalai PanbangredYasuhiro IgarashiTakuya NihiraShigeru KitaniToyama Prefectural UniversityOsaka UniversityMahidol University2022-08-042022-08-042021-01-01Journal of General and Applied Microbiology. Vol.67, No.6 (2021), 240-24713498037002212602-s2.0-85123389170https://repository.li.mahidol.ac.th/handle/20.500.14594/77336Streptomycetes 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.Mahidol UniversityImmunology and MicrobiologyArticleSCOPUS10.2323/jgam.2021.04.001