ABSTRACT
Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity. Previous structure‒activity relationships indicated that triple halogenated depsidones display the best anti-pathogenic activity. However, the gene cluster and the tailoring steps responsible for halogenated depsidone nornidulin ( 3) remain enigmatic. In this study, we disclosed the complete biosynthetic pathway of the halogenated depsidone through in vivo gene disruption, heterologous expression and in vitro biochemical experiments. We demonstrated an unusual depside skeleton biosynthesis process mediated by both highly-reducing polyketide synthase and non-reducing polyketide synthase, which is distinct from the common depside skeleton biosynthesis. This skeleton was subsequently modified by two in-cluster enzymes DepG and DepF for the ether bond formation and decarboxylation, respectively. In addition, the decarboxylase DepF exhibited substrate promiscuity for different scaffold substrates. Finally, and interestingly, we discovered a halogenase encoded remotely from the biosynthetic gene cluster, which catalyzes triple-halogenation to produce the active end product nornidulin ( 3). These discoveries provide new insights for further understanding the biosynthesis of depsidones and their derivatives.
ABSTRACT
Marine Actinobacteria are emerging as new resources for bioactive natural products with promise in novel drug discovery. In recent years, the richness and diversity of marine Actinobacteria from the South China Sea and their ability in producing bioactive products have been investigated. The objective of this work is to isolate and identify bioactive secondary metabolites from a marine actinobacterium SCSIO 1934 derived from sediments of South China Sea. The strain was identified as a Streptomyces spieces by analyzing its 16S rDNA sequence. Streptomyces sp. SCSIO 1934 was fermented under optimized conditions and seven bioactive secondary metabolites were isolated and purified by chromatographic methods including colum chromatography over silica gel and Sephadex LH-20. Their structures were elucidated as 17-O-demethylgeldanamycin (1), lebstatin (2), 17-O-demethyllebstatin (3), nigericin (4), nigericin sodium salt (5), abierixin (6), respectively, by detailed NMR spectroscopic data (1H, 13C, COSY, HSQC and HMBC). This work provided a new marine actinobacterium Streptomyces sp. SCSIO 1934, capable of producing diverse bioactive natural products.
Subject(s)
Anti-Bacterial Agents , Chemistry , China , DNA, Ribosomal , Chemistry , Genetics , Geologic Sediments , Microbiology , Oceans and Seas , RNA, Ribosomal, 16S , Genetics , Streptomyces , Chemistry , Classification , GeneticsABSTRACT
Aim To study the chemical constituents of Cypripedium tibeticum. Methods Compounds were isolated by repeated silica gel chromatography and purified on Sephadex LH-20 and structures were determined by spectral analysis. Results Cypritibetquinones A and B were isolated from the ethyl acetate residue and their structures were determined as 7-hydroxy-2-methoxy-1, 4-phenanthraquinone ( 1 ) and 7-hydroxy-2,10-dimethoxy-1,4-phenanthraquinone ( 2 ), respectively, by extensive spectral analyses. Conclusion Cypritibetquinones A and B are two new phenanthraquinones.
ABSTRACT
Objective To investigate the feasibility of cholangioenterostomy without stent tube drainage. (Methods) In this study 52 cases anastomosed without stent tube drainage (group A) and 56 cases with stent tube drainage (control,group B) were included. The patients′course of therapy and recovery, postoperative follow-up and reoperation were compared between group A and B. Results The rate of bile leakage was (5.8)% (3/52) in group A and 3.6%(2/56) in group B, respectively ,which was not significant(P