Cloning and identification of saprolmycin biosynthetic gene cluster from <i>Streptomyces</i> sp. TK08046

<p>Saprolmycins A–E are anti-<i>Saprolegnia parasitica</i> antibiotics. To identify the gene cluster for saprolmycin biosynthesis in <i>Streptomyces</i> sp. TK08046, polymerase chain reaction using aromatase and cyclase gene-specific primers was performed; the <i>spr</i> gene cluster, which codes for angucycline biosynthesis, was obtained from the strain. The cluster consists of 36 open reading frames, including minimal polyketide synthase, ketoreductase, aromatase, cyclase, oxygenase, and deoxy sugar biosynthetic genes, as defined by homology to the corresponding genes of the urdamycin, Sch-47554, and grincamycin biosynthetic gene clusters in <i>Streptomyces fradiae</i>, <i>Streptomyces</i> sp. SCC-2136, and <i>Streptomyces lusitanus</i>, respectively. To establish the function of the gene cluster, an expression cosmid vector containing all 36 open reading frames was introduced into <i>Streptomyces lividans</i> TK23. The transformant was confirmed to express the biosynthetic genes and produce saprolmycins by liquid chromatography–mass spectrometry analysis of the extract.</p> <p>We identified and cloned a <i>spr</i> gene cluster, which is involved in the biosynthesis of saprolmycin, and succeeded in heterologous production of saprolmycin.</p>