Mining the Cinnabaramide Biosynthetic Pathway to Generate Novel Proteasome Inhibitors

Rachid, Shwan; Huo, Liujie; Herrmann, Jennifer; Stadler, Marc; Köpcke, Bärbel; Bitzer, Jens; Müller, Rolf

doi:10.1002/cbic.201100024

Cited by 50 publications

(46 citation statements)

References 41 publications

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“…This gene is associated with the biosynthesis of salinosporamide A in S. tropica (6) and salinosporamide K in S. pacifica (7). The homolog cinA was recently identified in Streptomyces cinnabarinus as part of the pathway responsible for the biosynthesis of the salinosporamide-related cinnabaramide series (31). In total, the salA KS domain was detected in 15 of 61 S. pacifica strains, including 5 of 7 16S rRNA gene sequence types originating from three of the six locations sampled (Guam, Palau, and Fiji) ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

Evolution of Secondary Metabolite Genes in Three Closely Related Marine Actinomycete Species

Freel

Nam

Fenical

et al. 2011

Appl Environ Microbiol

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The marine actinomycete genus Salinispora is composed of three closely related species. These bacteria are a rich source of secondary metabolites, which are produced in species-specific patterns. This study examines the distribution and phylogenetic relationships of genes involved in the biosynthesis of secondary metabolites in the salinosporamide and staurosporine classes, which have been reported for S. tropica and S. arenicola, respectively. The focus is on "Salinispora pacifica," the most recently discovered and phylogenetically diverse member of the genus. Of 61 S. pacifica strains examined, 15 tested positive for a ketosynthase (KS) domain linked to the biosynthesis of salinosporamide K, a new compound in the salinosporamide series. Compound production was confirmed in two strains, and the domain phylogeny supports vertical inheritance from a common ancestor shared with S. tropica, which produces related compounds in the salinosporamide series. There was no evidence for interspecies recombination among salA KS sequences, providing further support for the geographic isolation of these two salinosporamide-producing lineages. In addition, staurosporine production is reported for the first time for S. pacifica, with 24 of 61 strains testing positive for staD, a key gene involved in the biosynthesis of this compound. High levels of recombination were observed between staD alleles in S. pacifica and the cooccurring yet more distantly related S. arenicola, which produces a similar series of staurosporines. The distributions and phylogenies of the biosynthetic genes examined provide insight into the complex processes driving the evolution of secondary metabolism among closely related bacterial species.

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Section: Resultsmentioning

confidence: 99%

Evolution of Secondary Metabolite Genes in Three Closely Related Marine Actinomycete Species

Freel

Nam

Fenical

et al. 2011

Appl Environ Microbiol

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“…These studies, along with the discovery of the related compounds cinnabaramides A–G and the associated biosynthetic pathway from a Streptomyces sp. 67, 68 , provided some of the first evidence of the evolutionary complexity associated with secondary metabolism in Salinispora species. The sal pathway has more recently been detected in a limited number of S. arenicola strains 33, 44 although compound production appears to be very low in this species (unpublished data).…”

Section: Salinispora Natural Productsmentioning

confidence: 99%

The marine actinomycete genus Salinispora: a model organism for secondary metabolite discovery

2015

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This review covers the initial discovery of the marine actinomycete genus Salinispora through its development as a model for natural product research. A focus is placed on the novel chemical structures reported with reference to their biological activities and the synthetic and biosynthetic studies they have inspired. The time line of discoveries progresses from more traditional bioassay-guided approaches through the application of genome mining and genetic engineering techniques that target the products of specific biosynthetic gene clusters. This overview exemplifies the extraordinary biosynthetic diversity that can emanate from a narrowly defined genus and supports future efforts to explore marine taxa in the search for novel natural products.

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“…A homolog of the latter enzyme was also shown to be responsible for the synthesis of the unusual extender units chloroethylmalonyl-CoA (from chlorocrotonyl-CoA) and propylmalonyl-CoA (from 2-pentenylCoA) (46,80). Moreover, in the biosynthesis of the proteasome inhibitor cinnabaramide A and the macrolide antibiotic filipin, CCR homologs supply hexylmalonyl-CoA via reductive carboxylation of 2-octenoyl-CoA (97,112,130).…”

Section: Carboxylases In Biosynthetic Pathwaysmentioning

confidence: 99%

Carboxylases in Natural and Synthetic Microbial Pathways

Erb

2011

Appl Environ Microbiol

182

165

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Carboxylases are among the most important enzymes in the biosphere, because they catalyze a key reaction in the global carbon cycle: the fixation of inorganic carbon (CO 2 ). This minireview discusses the physiological roles of carboxylases in different microbial pathways that range from autotrophy, carbon assimilation, and anaplerosis to biosynthetic and redox-balancing functions. In addition, the current and possible future uses of carboxylation reactions in synthetic biology are discussed. Such uses include the possible transformation of the greenhouse gas carbon dioxide into value-added compounds and the production of novel antibiotics.

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Mining the Cinnabaramide Biosynthetic Pathway to Generate Novel Proteasome Inhibitors

Abstract: JournalChembiochem : a European journal of chemical biology

Cited by 50 publications

References 41 publications

Evolution of Secondary Metabolite Genes in Three Closely Related Marine Actinomycete Species

Evolution of Secondary Metabolite Genes in Three Closely Related Marine Actinomycete Species

The marine actinomycete genus Salinispora: a model organism for secondary metabolite discovery

Carboxylases in Natural and Synthetic Microbial Pathways

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