Tohyama Shigehiro, Kakinuma Katsumi, Eguchi Tadashi
Department of Chemistry & Materials Science, Tokyo Institute of Technology, 2-12-1, O-okayama, Meguro-ku, Tokyo 152-8551, Japan.
J Antibiot (Tokyo). 2006 Jan;59(1):44-52. doi: 10.1038/ja.2006.7.
Halstoctacoanolides A and B are 28-membered polyketide macrolactones and were isolated from Streptomyces halstedii HC34. The biosynthetic gene cluster (hls cluster) of halstoctacosanolides was completely identified from the genome library of Streptomyces halstedii HC34. DNA sequence analysis of ca. 100 kb region revealed that there were seven type I polyketide synthases (PKSs) and two cytochrome P450 monooxygenases in this cluster. Involvement of the gene cluster in the halstoctacosanolide biosynthesis was demonstrated by the gene disruption of P450 monooxygenase genes. The mutants produced a new deoxygenated halstoctacosanolide derivative, halstoctacosanolide C, which confirmed that the hls gene cluster was essential for the biosynthesis of halstoctacosanolides.
哈尔斯托他醇内酯A和B是28元聚酮大环内酯类化合物,从哈氏链霉菌HC34中分离得到。从哈氏链霉菌HC34的基因组文库中完全鉴定出了哈尔斯托他醇内酯的生物合成基因簇(hls基因簇)。对约100 kb区域的DNA序列分析表明,该基因簇中有7个I型聚酮合酶(PKS)和2个细胞色素P450单加氧酶。通过对P450单加氧酶基因的基因敲除证明了该基因簇参与哈尔斯托他醇内酯的生物合成。突变体产生了一种新的脱氧哈尔斯托他醇内酯衍生物——哈尔斯托他醇内酯C,这证实了hls基因簇对哈尔斯托他醇内酯的生物合成至关重要。