title: Cloning, characterization and heterologous expression of the indolocarbazole biosynthetic gene cluster from marine-derived Streptomyces sanyensis FMA.
abstract: The indolocarbazole (ICZ) alkaloids have attracted much attention due to their unique structures and potential therapeutic applications. A series of ICZs were recently isolated and identified from a marine-derived actinomycete strain, Streptomyces sanyensis FMA. To elucidate the biosynthetic machinery associated with ICZs production in  S. sanyensis FMA, PCR using degenerate primers was carried out to clone the FAD-dependent monooxygenase gene fragment for ICZ ring formation, which was used as a probe to isolate the 34.6-kb DNA region containing the spc gene cluster. Sequence analysis revealed genes for ICZ ring formation (spcO, D, P, C), sugar unit formation (spcA, B, E, K,  J, I), glycosylation (spcN, G), methylation (spcMA, MB), as well as regulation (spcR). Their involvement in ICZ biosynthesis was confirmed by gene inactivation and heterologous expression in Streptomyces coelicolor M1152. This work represents the first cloning and characterization of an ICZ gene cluster isolated from a marine-derived actinomycete strain and would be helpful for thoroughly understanding the biosynthetic mechanism of  ICZ glycosides.
authors: Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors: Tong
authors: T
authors: Li
authors: Yuanyuan
authors: Y
authors: Du
authors: Qiu
authors: Q
authors: Cui
authors: Jingtao
authors: J
authors: Zhang
authors: Weiming
authors: W
authors: Zhu
authors: Kui
authors: K
authors: Hong
authors: Wenli
authors: W
authors: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D004269:DNA, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family; D010957:Plasmids; D013302:Streptomyces / Q000145:classification* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002227:Carbazoles; D004269:DNA, Bacterial
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