Kalan Lindsay, Gessner Arne, Thaker Maulik N, Waglechner Nicholas, Zhu Ximing, Szawiola Anjuli, Bechthold Andreas, Wright Gerard D, Zechel David L
Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Chem Biol. 2013 Oct 24;20(10):1214-24. doi: 10.1016/j.chembiol.2013.09.006. Epub 2013 Oct 10.
Streptomyces calvus is best known as the producer of the fluorinated natural product nucleocidin. This strain of Streptomycetes is also unusual for displaying a "bald" phenotype that is deficient in the formation of aerial mycelium and spores. Genome sequencing of this organism revealed a point mutation in the bldA gene that is predicted to encode a misfolded Leu-tRNA(UUA) molecule. Complementation of S. calvus with a correct copy of bldA restored sporulation and additionally promoted production of a polyeneoic acid amide, 4-Z-annimycin, and a minor amount of the isomer, 4-E-annimycin. Bioassays reveal that these compounds inhibit morphological differentiation in other Actinobacteria. The annimycin gene cluster encoding a type 1 polyketide synthase was identified and verified through disruption studies. This study underscores the importance of the bldA gene in regulating the expression of cryptic biosynthetic genes.
光滑链霉菌最为人所知的是其作为氟化天然产物核苷菌素的生产者。这种链霉菌菌株也很不寻常，因为它表现出一种“光秃”表型，即气生菌丝体和孢子形成不足。对该生物体的基因组测序揭示了bldA基因中的一个点突变，预计该突变会编码一个错误折叠的亮氨酸tRNA（UUA）分子。用正确的bldA拷贝对光滑链霉菌进行互补恢复了孢子形成，此外还促进了多烯酸酰胺4-Z-安尼霉素以及少量异构体4-E-安尼霉素的产生。生物测定表明，这些化合物抑制其他放线菌中的形态分化。通过基因敲除研究鉴定并验证了编码1型聚酮合酶的安尼霉素基因簇。这项研究强调了bldA基因在调节隐性生物合成基因表达中的重要性。
