scholarly journals Coupled Biosynthesis of Volatiles and Salinosporamide A in Salinispora tropica

ChemBioChem ◽  
2016 ◽  
Vol 17 (20) ◽  
pp. 1978-1985 ◽  
Author(s):  
Ulrike Groenhagen ◽  
Ana Ligia Leandrini De Oliveira ◽  
Elisha Fielding ◽  
Bradley S. Moore ◽  
Stefan Schulz
Keyword(s):  
Salinosporamide A ◽  
Salinispora Tropica

Exploration and engineering of biosynthetic pathways in the marine actinomycete Salinispora tropica

2009 ◽  
Vol 81 (6) ◽  
pp. 1075-1084 ◽  
Author(s):  
Markus Nett ◽  
Bradley S. Moore
Keyword(s):  
Natural Products ◽  
Metabolic Pathways ◽  
Anticancer Agent ◽  
Complex Molecules ◽  
Dna Cleaving ◽  
Metabolic Plasticity ◽  
Salinosporamide A ◽  
Salinispora Tropica ◽  
Marine Actinomycete ◽  
Key Genes

In recent years, members of the marine actinomycete genus Salinispora have proven to be a precious source of structurally diverse secondary metabolites, including the potent anticancer agent salinosporamide A and the enediyne-derived sporolides. The tremendous potential of these marine-dwelling microbes for natural products biosynthesis, however, was not fully realized until sequencing of the Salinispora tropica genome revealed the presence of numerous orphan biosynthetic loci besides a plethora of rare metabolic pathways. This contribution summarizes the biochemical exploration of this prolific organism, highlighting studies in which genome-based information was exploited for the discovery of new enzymatic processes and the engineering of unnatural natural products. Inactivation of key genes within the salinosporamide pathway has expanded its inherent metabolic plasticity and enabled access to various salinosporamide derivatives by mutasynthesis. New insights into the biosynthesis of the sporolides allowed us to increase production titers of these structurally complex molecules, thereby providing the means to search for the DNA cleaving presporolide enediyne.

scholarly journals Antileukemic Activity and Mechanism of Drug Resistance to the Marine Salinispora tropica Proteasome Inhibitor Salinosporamide A (Marizomib)

2014 ◽  
Vol 86 (1) ◽  
pp. 12-19 ◽  
Author(s):  
Denise Niewerth ◽  
Gerrit Jansen ◽  
Lesley F. V. Riethoff ◽  
Johan van Meerloo ◽  
Andrew J. Kale ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Proteasome Inhibitor ◽  
Antileukemic Activity ◽  
Salinosporamide A ◽  
Salinispora Tropica

scholarly journals Comparison of biochemical and biological effects of ML858 (salinosporamide A) and bortezomib

2006 ◽  
Vol 5 (12) ◽  
pp. 3052-3061 ◽  
Author(s):  
Mark J. Williamson ◽  
Jonathan L. Blank ◽  
Frank J. Bruzzese ◽  
Yueying Cao ◽  
J. Scott Daniels ◽  
...  
Keyword(s):  
Biological Effects ◽  
Salinosporamide A

scholarly journals Back Cover: Total Synthesis of (−)‐Salinosporamide A via a Late Stage C−H Insertion (Angew. Chem. Int. Ed. 30/2019)

2019 ◽  
Vol 58 (30) ◽  
pp. 10376-10376
Author(s):  
Hadi Gholami ◽  
Aman Kulshrestha ◽  
Olivia K. Favor ◽  
Richard J. Staples ◽  
Babak Borhan
Keyword(s):  
Total Synthesis ◽  
Late Stage ◽  
Back Cover ◽  
Salinosporamide A

scholarly journals Phytoplankton trigger the production of cryptic metabolites in the marine actinobacteria Salinispora tropica

2020 ◽  
Author(s):  
Audam Chhun ◽  
Despoina Sousoni ◽  
Maria del Mar Aguiló-Ferretjans ◽  
Lijiang Song ◽  
Christophe Corre ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Antibiotic Production ◽  
Antimicrobial Effect ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Marine Actinobacteria ◽  
Salinispora Tropica ◽  
Eukaryotic Phytoplankton

AbstractBacteria from the Actinomycete family are a remarkable source of natural products with pharmaceutical potential. The discovery of novel molecules from these organisms is, however, hindered because most of the biosynthetic gene clusters (BGCs) encoding these secondary metabolites are cryptic or silent and are referred to as orphan BGCs. While co-culture has proven to be a promising approach to unlock the biosynthetic potential of many microorganisms by activating the expression of these orphan BGCs, it still remains an underexplored technique. The marine actinobacteria Salinispora tropica, for instance, produces valuable compounds such as the anti-cancer molecule salinosporamide A but half of its putative BGCs are still orphan. Although previous studies have looked into using marine heterotrophs to induce orphan BGCs in Salinispora, the potential impact of co-culturing marine phototrophs with Salinispora has yet to be investigated. Following the observation of clear antimicrobial phenotype of the actinobacterium on a range of phytoplanktonic organisms, we here report the discovery of novel cryptic secondary metabolites produced by S. tropica in response to its co-culture with photosynthetic primary producers. An approach combining metabolomics and proteomics revealed that the photosynthate released by phytoplankton influences the biosynthetic capacities of S. tropica with both production of new molecules and the activation of orphan BGCs. Our work pioneers the use of phototrophs as a promising strategy to accelerate the discovery of novel natural products from actinobacteria.ImportanceThe alarming increase of antimicrobial resistance has generated an enormous interest in the discovery of novel active compounds. The isolation of new microbes to untap novel natural products is currently hampered because most biosynthetic gene clusters (BGC) encoded by these microorganisms are not expressed under standard laboratory conditions, i.e. mono-cultures. Here we show that co-culturing can be an easy way for triggering silent BGC. By combining state-of-the-art metabolomics and high-throughput proteomics, we characterized the activation of cryptic metabolites and silent biosynthetic gene clusters in the marine actinobacteria Salinispora tropica by the presence of phytoplankton photosynthate. We further suggest a mechanistic understanding of the antimicrobial effect this actinobacterium has on a broad range of prokaryotic and eukaryotic phytoplankton species and reveal a promising candidate for antibiotic production.

scholarly journals Synthetic studies of salinosporamide A through the intramolecular hydroamidation of alkynes

2011 ◽  
Vol 696 (1) ◽  
pp. 42-45 ◽  
Author(s):  
Haruhi Kamisaki ◽  
Yusuke Kobayashi ◽  
Tetsutaro Kimachi ◽  
Yoshizumi Yasui ◽  
Yoshiji Takemoto
Keyword(s):  
Salinosporamide A ◽  
Synthetic Studies

scholarly journals Diastereoselective Synthesis of Fused Lactone-Pyrrolidinones; Application to a Formal Synthesis of (−)-Salinosporamide A

2014 ◽  
Vol 16 (16) ◽  
pp. 4078-4081 ◽  
Author(s):  
Angus W. J. Logan ◽  
Simon J. Sprague ◽  
Robert W. Foster ◽  
Léo B. Marx ◽  
Vincenzo Garzya ◽  
...  
Keyword(s):  
Diastereoselective Synthesis ◽  
Formal Synthesis ◽  
Salinosporamide A
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