Genetic organization of the biosynthetic gene cluster for the indolocarbazole K-252a in Nonomuraea longicatena JCM 11136 |
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Authors: | Seung-Young Kim Jin-Soo Park Choong-Sik Chae Chang-Gu Hyun Byoung Wook Choi Jongheon Shin Ki-Bong Oh |
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Affiliation: | (1) Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-921, South Korea;(2) Laboratory for Advanced Materials, Biospectrum, Jeju Bio-Industry Development Center R204, Jeju, 690-121, South Korea;(3) Department of Applied Chemistry, Hanbat National University, Daejeon, 305-719, South Korea;(4) Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, 110-460, South Korea;(5) Center for Agricultural Biomaterials, Seoul National University, Seoul, 151-921, South Korea |
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Abstract: | Indolocarbazole metabolite K-252a is a natural product that was previously reported as a potent protein kinase C inhibitor with in vitro and in vivo potency. From a biosynthetic viewpoint, this compound possesses structurally interesting features such as an unusual furanosyl sugar moiety, which are absent in the well-studied staurosporine and rebeccamycin. A cosmid library from genomic DNA of Nonomuraea longicatena JCM 11136 was constructed and screened for the presence of genes to be involved in the biosynthesis of indolocarbazole K-252a. Using as a probe an internal fragment of vioB, a Chromobacterium violaceum gene encoding a multifunctional enzyme that catalyzes tryptophan decarboxylation and condensation reaction in violacein biosynthesis, we isolated a DNA region that directed the biosynthesis of K-252a when introduced into the heterologous expression host Streptomyces albus. Sequence analysis of 45 kb revealed genes for indolocarbazole core formation, glycosylation, and sugar methylation, as well as a regulatory gene and two resistance/secretion genes. The cloned genes should help to elucidate the molecular basis for indolocarbazole biosynthesis and generate new indolocarbazole analogues by genetic engineering. |
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Keywords: | Nonomuraea longicatena Indolocarbazole K-252a Biosynthesis Gene cluster Heterologous expression |
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