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Mar. Drugs 2013, 11(2), 466-488; doi:10.3390/md11020466

Cloning, Characterization and Heterologous Expression of the Indolocarbazole Biosynthetic Gene Cluster from Marine-Derived Streptomyces sanyensis FMA

1
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
2
Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, No. 189 Songling Road, Qingdao 266101, China
3
Ministry of Education of China, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
*
Authors to whom correspondence should be addressed.
Received: 21 November 2012 / Revised: 24 December 2012 / Accepted: 21 January 2013 / Published: 6 February 2013
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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.
Keywords: indolocarbazole (ICZ); biosynthesis; heterologous expression; Streptomyces sanyensis FMA indolocarbazole (ICZ); biosynthesis; heterologous expression; Streptomyces sanyensis FMA
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Li, T.; Du, Y.; Cui, Q.; Zhang, J.; Zhu, W.; Hong, K.; Li, W. Cloning, Characterization and Heterologous Expression of the Indolocarbazole Biosynthetic Gene Cluster from Marine-Derived Streptomyces sanyensis FMA. Mar. Drugs 2013, 11, 466-488.

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