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Tan, RX, Jensen PR, Williams PG, Fenical W.  2004.  Isolation and structure assignments of rostratins A-D, cytotoxic disulfides produced by the marine-derived fungus Exserohilum rostratum. Journal of Natural Products. 67:1374-1382.   10.1021/np049920b   AbstractWebsite

Four new cytotoxic disulfides, rostratins A-D (1-4), were isolated from the whole broth of the marine-derived fungus Exserohilum rostratum (Drechsler), a fungal strain found associated with a marine cyanobacterial mat. The structures of these cyclic dipeptides were established through chemical degradation and a variety of two-dimensional NMR techniques. The absolute configurations of the rostratins were determined by the modified Mosher method. In the case of the polyhydroxylated compound 1 and the mercaptol 4, regioselective acylation was achieved by modulating the reaction temperature while monitoring the progress of the reaction by H-1 NMR. Rostratins A, B, C, and D showed in vitro cytotoxicity against human colon carcinoma (HCT-116) with IC50 values of 8.5, 1.9, 0.76, and 16.5 mug/mL, respectively.

Tan, LT, Cheng XC, Jensen PR, Fenical W.  2003.  Scytalidamides A and B, new cytotoxic cyclic heptapeptides from a marine fungus of the genus Scytalidium. Journal of Organic Chemistry. 68:8767-8773.   10.1021/jo030191z   AbstractWebsite

Two new cyclic heptapeptides have been isolated from the culture broth of a marine fungus, Scytalidium sp., collected from the Bahamas. The planar structures of scytalidamides A (1) and B (2) were assigned on the basis of 1D and 2D NMR spectroscopic techniques, while the absolute configuration of the amino acid residues in both molecules was determined by application of the advanced Mar-fey's method. The absolute stereochemistry of the uncommon 3-methylproline moiety in scytalidamide B (2) was confirmed by isolation and CD measurements, as well as application of the advanced Marfey's method. Scytalidamides A (1) and B (2) showed moderate in vitro cytotoxicity toward HCT-116 human colon adenocarcinoma with IC50 values of 2.7 and 11.0 muM, respectively.

Tang, XY, Li J, Millan-Aguinaga N, Zhang JJ, O'Neill EC, Ugalde JA, Jensen PR, Mantovani SM, Moore BS.  2015.  Identification of thiotetronic acid antibiotic biosynthetic pathways by target-directed genome mining. Acs Chemical Biology. 10:2841-2849.   10.1021/acschembio.5b00658   AbstractWebsite

Recent genome sequencing efforts have led to the rapid accumulation of uncharacterized or "orphaned" secondary metabolic biosynthesis gene clusters (BGCs) in public databases. This increase in DNA-sequenced big data has given rise to significant challenges in the applied field of natural product genome mining, including (i) how to prioritize the characterization of orphan BGCs and (ii) how to rapidly connect genes to biosynthesized small molecules. Here, we show that by correlating putative antibiotic resistance genes that encode target-modified proteins with orphan BGCs, we predict the biological function of pathway specific small molecules before they have been revealed in a process we call target-directed genome mining. By querying the pan-genome of 86 Salinispora bacterial genomes for duplicated house-keeping genes colocalized with natural product BGCs, we prioritized an orphan polyketide synthase-nonribosomal peptide synthetase hybrid BGC (tlm) with a putative fatty acid synthase resistance gene. We employed a new synthetic double-stranded DNA-mediated cloning strategy based on transformation-associated recombination to efficiently capture tlm and the related Mu BGCs directly from genomic DNA and to heterologously express them in Streptomyces hosts. We show the production of a group of unusual thiotetronic acid natural products, including the well-known fatty acid synthase inhibitor thiolactomycin that was first described over 30 years ago, yet never at the genetic level in regards to biosynthesis and autoresistance. This finding not only validates the target-directed genome mining strategy for the discovery of antibiotic producing gene clusters without a priori knowledge of the molecule synthesized but also paves the way for the investigation of novel: enzymology involved in thiotetronic, acid natural product biosynthesis.

Toske, SG, Jensen PR, Kauffman CA, Fenical W.  1995.  Elijopyrones a-D - New Alpha-Pyrones from a Marine Actinomycete. Natural Product Letters. 6:303-308.   10.1080/10575639508043175   AbstractWebsite

Elijopyrones A-D (1-4) were isolated from a cultured marine actinomycete (isolate CNB-880). The producing strain was obtained from a sediment collected from the San Elijo Lagoon, Cardiff, California. The structures of the new compounds were determined by comprehensive spectral analyses.

Toske, SG, Jensen PR, Kauffman CA, Fenical W.  1998.  Aspergillamides A and B: Modified cytotoxic tripeptides produced by a marine fungus of the genus Aspergillus. Tetrahedron. 54:13459-13466.   10.1016/s0040-4020(98)00829-1   AbstractWebsite

Two isomeric linear peptides, aspergillamides A and B (1, 2), were isolated from the mycelium of a cultured marine fungus of the genus Aspergillus. The producing strain (designated CNC-120), was obtained from a saline lake sediment sample collected from Acklins Island. the Bahamas. The structures of the new peptides were elucidated using comprehensive 2D NMR methods. At 25 degrees C, in both acetone and dimethylsulfoxide, aspergillamide A exists as a 1:1 mixture of trans- and cis-amide rotational isomers (1a and 1b). Under identical conditions, aspergillamide B is predominantly in the cis-amide form. The absolute stereochemistries of the amino acids in aspergillamide A were assigned as L by hydrolysis and comparison with commercial standards. Aspergillamide A showed modest irt virro cytotoxicity [IC50 = 16 mu g/ml] toward the human colon carcinoma cell line HCT-116. (C) 1998 Elsevier Science Ltd. All rights reserved.

Trischman, JA, Tapiolas DM, Jensen PR, Dwight R, Fenical W, McKee TC, Ireland CM, Stout TJ, Clardy J.  1994.  Salinamide-a and Salinamide-B - Antiinflammatory Depsipeptides from a Marine Streptomycete. Journal of the American Chemical Society. 116:757-758.   10.1021/ja00081a042   Website
Trischman, JA, Jensen PR, Fenical W.  1998.  Guaymasol and epiguaymasol: Aromatic triols from a deep-sea Bacillus isolate. Natural Product Letters. 11:279-284.   10.1080/10575639808044960   AbstractWebsite

Two new aromatic compounds, guaymasol (1) and epiguaymasol (2), have been isolated from cultures of a Bacillus species (isolate CNA-995) taken from a deep-sea sediment core. The structures, including relative stereochemistry, were assigned on the basis of spectral analyses of the natural products and their acetonide derivatives.

Trischman, JA, Jensen PR, Fenical W.  1994.  Halobacillin - a Cytotoxic Cyclic Acylpeptide of the Iturin Class Produced by a Marine Bacillus. Tetrahedron Letters. 35:5571-5574.   10.1016/s0040-4039(00)77249-2   AbstractWebsite

Halobacillin (1), a new cyclic acylpeptide of the iturin class, has been isolated from cultures of a Bacillus species (culture # CND-914) obtained from a deep-sea sediment core. The structure of the new compound was assigned on the basis of comprehensive NMR studies of 1 and methyl halobacillin (2), and evaluation of the amino acids obtained by acid hydrolysis.

Tuttle, RN, Demko AM, Patin NV, Kapono CA, Donia MS, Dorrestein P, Jensen PR.  2019.  Detection of natural products and their producers in ocean sediments. Applied and Environmental Microbiology. 85   10.1128/aem.02830-18   AbstractWebsite

Thousands of natural products have been identified from cultured microorganisms, yet evidence of their production in the environment has proven elusive. Technological advances in mass spectrometry, combined with public data-bases, now make it possible to address this disparity by detecting compounds directly from environmental samples. Here, we used adsorbent resins, tandem mass spectrometry, and next-generation sequencing to assess the metabolome of marine sediments and its relationship to bacterial community structure. We identified natural products previously reported from cultured bacteria, providing evidence they are produced in situ, and compounds of anthropogenic origin, suggesting this approach can be used as an indicator of environmental impact. The bacterial metabolite staurosporine was quantified and shown to reach physiologically relevant concentrations, indicating that it may influence sediment community structure. Staurosporine concentrations were correlated with the relative abundance of the staurosporine-producing bacterial genus Salinispora and production confirmed in strains cultured from the same location, providing a link between compound and candidate producer. Metagenomic analyses revealed numerous biosynthetic gene clusters related to indolocarbazole biosynthesis, providing evidence for noncanonical sources of staurosporine and a path forward to assess the relationships between natural products and the organisms that produce them. Untargeted environmental metabolomics circumvents the need for laboratory cultivation and represents a promising approach to understanding the functional roles of natural products in shaping microbial community structure in marine sediments. IMPORTANCE Natural products are readily isolated from cultured bacteria and exploited for useful purposes, including drug discovery. However, these compounds are rarely detected in the environments from which the bacteria are obtained, thus limiting our understanding of their ecological significance. Here, we used environmental metabolomics to directly assess chemical diversity in marine sediments. We identified numerous metabolites and, in one case, isolated strains of bacteria capable of producing one of the compounds detected. Coupling environmental metabolomics with community and metagenomic analyses provides opportunities to link compounds and producers and begin to assess the complex interactions mediated by specialized metabolites in marine sediments.