Publications

Export 14 results:
Sort by: [ Author  (Asc)] Title Type Year
A B C D E F G H I J K L [M] N O P Q R S T U V W X Y Z   [Show ALL]
M
Machado, H, Tuttle RN, Jensen PR.  2017.  Omics-based natural product discovery and the lexicon of genome mining. Current Opinion in Microbiology. 39:136-142.   10.1016/j.mib.2017.10.025   AbstractWebsite

Genome sequencing and the application of omic techniques are driving many important advances in the field of microbial natural products research. Despite these gains, there remain aspects of the natural product discovery pipeline where our knowledge remains poor. These include the extent to which biosynthetic gene clusters are transcriptionally active in native microbes, the temporal dynamics of transcription, translation, and natural product assembly, as well as the relationships between small molecule production and detection. Here we touch on a number of these concepts in the context of continuing efforts to unlock the natural product potential revealed in genome sequence data and discuss nomenclatural issues that warrant consideration as the field moves forward.

Macherla, VR, Mitchell SS, Manam RR, Reed KA, Chao TH, Nicholson B, Deyanat-Yazdi G, Mai B, Jensen PR, Fenical WF, Neuteboom STC, Lam KS, Palladino MA, Potts BCM.  2005.  Structure-activity relationship studies of salinosporamide a (NPI-0052), a novel marine derived proteasome inhibitor. Journal of Medicinal Chemistry. 48:3684-3687.   10.1021/jm048995+   AbstractWebsite

Salinosporamide A (1, NPI-0052) is a potent proteasome inhibitor in development for treating cancer. In this study, a series of analogues was assayed for cytotoxicity, proteasome inhibition, and inhibition of NF-kappa B activation. Marked reductions in potency in cell-based assays accompanied replacement of the chloroethyl group with unhalogenated substituents. Halogen exchange and cyclohexene ring epoxidation were well tolerated, while some stereochemical modifications significantly attenuated activity. These findings provide insights into structure-activity relationships within this novel series.

Maldonado, LA, Fenical W, Jensen PR, Kauffman CA, Mincer TJ, Ward AC, Bull AT, Goodfellow M.  2005.  Salinispora arenicola gen. nov., sp nov and Salinispora tropica sp nov., obligate marine actinomycetes belonging to the family Micromonosporaceae. International Journal of Systematic and Evolutionary Microbiology. 55:1759-1766.   10.1099/ijs.0.63625-0   AbstractWebsite

A taxonomic study was carried out to clarify the taxonomy of representatives of a group of marine actinomycetes previously designated MAR 1 and considered to belong to the family Micromonosporaceae. The organisms had phenotypic properties consistent with their assignment to this taxon. The strains formed a distinct taxon in the 16S rRNA Micromonosporaceae gene tree and shared a range of phenotypic properties that distinguished them from members of all of the genera with validly published names classified in this family. The name proposed for this novel taxon is Salinispora gen. nov. The genus contains two species recognized using a range of genotypic and phenotypic criteria, including comparative 16S-23S rRNA gene spacer region and DNA-DNA relatedness data. The names proposed for these taxa are Salinispora arenicola sp. nov., the type species, and Salinispora tropica sp. nov., the type strains of these novel species have been deposited in service culture collections as strain CNH-643(T) ( = ATCC BAA-917(T) = DSM 44819(T)) and strain CNB-440(T) ( = ATCC BAA-916(T) = DSM 44818(T)), respectively.

Maloney, KN, MacMillan JB, Kauffman CA, Jensen PR, DiPasquale AG, Rheingold AL, Fenical W.  2009.  Lodopyridone, a Structurally Unprecedented Alkaloid from a Marine Actinomycete. Organic Letters. 11:5422-5424.   10.1021/ol901997k   AbstractWebsite

Chemical examination of the secondary metabolites of a marine Saccharomonospora sp., isolated from marine sediments collected at the mouth of the La Jolla Submarine Canyon, yielded the unprecedented alkaloid lodopyridone (1). The low proton-to-carbon ratio of 1 precluded structure elucidation by NMR spectroscopic methods, thus the structure was defined by X-ray crystallography. Lodopyridone is cytotoxic to HCT-116 human colon cancer cells with IC(50) = 3.6 mu M.

Martin, GDA, Tan LT, Jensen PR, Dimayuga RE, Fairchild CR, Raventos-Suarez C, Fenical W.  2007.  Marmycins a and b, cytotoxic pentacyclic c-glycosides from a marine sediment-derived actinomycete related to the genus Streptomyces. Journal of Natural Products. 70:1406-1409.   10.1021/np06062lr   AbstractWebsite

Two new cytotoxic quinones of the angucycline class, marmycins A and B (1, 2), were isolated from the culture broth of a marine sediment-derived actinomycete related to the genus Streptomyces. The gross structures and absolute configurations of both compounds were determined by spectroscopic and crystallographic methods. Marmycin A (1) displayed significant cytotoxicity against several cancer cell lines, some at nanomolar concentrations; while compound 2, a chloro analogue of 1, was less potent. For marmycin A (1), tumor cell cytotoxicity appeared to coincide with induction of modest apoptosis and arrest in the G1 phase of the cell cycle.

Meyer, SW, Mordhorst TF, Lee C, Jensen PR, Fenical W, Kock M.  2010.  Penilumamide, a novel lumazine peptide isolated from the marine-derived fungus, Penicillium sp CNL-338. Organic & Biomolecular Chemistry. 8:2158-2163.   10.1039/b910629d   AbstractWebsite

A novel lumazine peptide, penilumamide (1), was isolated from the fermentation broth of a marine-derived fungal strain, identified as Penicillium sp. (strain CNL-338) and the structure of the new metabolite was determined by analysis of ESI-TOF MS data combined with 1D and 2D NMR experiments.

Millan-Aguinaga, N, Chavarria KL, Ugalde JA, Letzel AC, Rouse GW, Jensen PR.  2017.  Phylogenomic Insight into Salinispora (Bacteria, Actinobacteria) Species Designations. Scientific Reports. 7   10.1038/s41598-017-02845-3   AbstractWebsite

Bacteria represent the most genetically diverse kingdom of life. While great progress has been made in describing this diversity, it remains difficult to identify the phylogenetic and ecological characteristics that delineate groups of bacteria that possess species-like properties. One major challenge associated with species delineations is that not all shared genes have the same evolutionary history, and thus the choice of loci can have a major impact on phylogenetic reconstruction. Sequencing the genomes of large numbers of closely related strains provides new opportunities to distinguish ancestral from acquired alleles and assess the effects of recombination on phylogenetic inference. Here we analyzed the genomes of 119 strains of the marine actinomycete genus Salinispora, which is currently comprised of three named species that share 99% 16S rRNA gene sequence identity. While 63% of the core genome showed evidence of recombination, this had no effect on species-level phylogenomic resolution. Recombination did however blur intra-species relationships and biogeographic resolution. The genome-wide average nucleotide identity provided a new perspective on Salinispora diversity, revealing as many as seven new species. Patterns of orthologous group distributions reveal a genetic basis to delineation the candidate taxa and insight into the levels of genetic cohesion associated with bacterial species.

Miller, ED, Kauffman CA, Jensen PR, Fenical W.  2007.  Piperazimycins: Cytotoxic hexadepsipeptides from a marine-derived bacterium of the genus Streptomyces. Journal of Organic Chemistry. 72:323-330.   10.1021/jo061064g   AbstractWebsite

[graphics] Three potent cancer cell cytotoxins, piperazimycins A-C (1-3), have been isolated from the fermentation broth of a Streptomyces sp., cultivated from marine sediments near the island of Guam. The structures of these cyclic hexadepsipeptides were assigned by a combination of spectral, chemical, and crystallographic methods. The piperazimycins are composed of rare amino acids, including hydroxyacetic acid, alpha-methylserine, gamma-hydroxypiperazic acid, and gamma-chloropiperazic acid. The novel amino acid residues 2-amino-8-methyl-4,6-nonadienoic acid and 2-amino-8-methyl-4,6-decadienoic acid were found as components of piperazimycins A and C, respectively. When screened in the National Cancer Institute's 60 cancer cell line panel, piperazimycin A exhibited potent in vitro cytotoxicity toward multiple tumor cell lines with a mean GI(50) of 100 nM.

Mincer, TJ, Spyere A, Jensen PR, Fenical W.  2004.  Phylogenetic analyses and diterpenoid production by marine bacteria of the genus saprospira. Current Microbiology. 49:300-307.   10.1007/s00284-004-4358-8   AbstractWebsite

The relationship between 16S rRNA gene sequence-derived phylogeny and the bacterial production of diterpenoids from 18 isolates of marine bacteria belonging to the genus Saprospira was determined. Restriction fragment length polymorphism (RFLP) analysis of the PCR amplified 16S rRNA genes of these isolates indicated four distinct phylotypes. The terpenoid metabolite profiles of each phylotype, determined by liquid chromatography mass spectrometry (LCMS) and nuclear magnetic resonance (NMR) analyses, indicated that diterpenoid production was restricted to phylotype A, which included the type specimen S. grandis Gross, and the sole member of the closely related phylotype B. The discovery of two new neoverrucosane diterpenoids produced by phylotype B has also been documented.

Mincer, TJ, Fenical W, Jensen PR.  2005.  Culture-dependent and culture-independent diversity within the obligate marine actinomycete genus Salinispora. Applied and Environmental Microbiology. 71:7019-7028.   10.1128/aem.71.11.7019-7028.2005   AbstractWebsite

Salinispora is the first obligate marine genus within the order Actinomycetales and a productive source of biologically active secondary metabolites. Despite a worldwide, tropical or subtropical distribution in marine sediments, only two Salinispora species have thus far been cultivated, suggesting limited species-level diversity. To further explore Salinispora diversity and distributions, the phylogenetic diversity of more than 350 strains isolated from sediments collected around the Bahamas was examined, including strains cultured using new enrichment methods. A culture-independent method, using a Salinispora-specific seminested PCR technique, was used to detect Salinispora from environmental DNA and estimate diversity. Overall, the 16S rRNA gene sequence diversity of cultured strains agreed well with that detected in the environmental clone libraries. Despite extensive effort, no new species level diversity was detected, and 97% of the 105 strains examined by restriction fragment length polymorphism belonged to one phylotype (S. arenicola). New intraspecific diversity was detected in the libraries, including an abundant new phylotype that has yet to be cultured, and a new depth record of 1,100 m was established for the genus. PCR-introduced error, primarily from Taq polymerase, significantly increased clone library sequence diversity and, if not masked from the analyses; would have led to an overestimation of total diversity. An environmental DNA extraction method specific for vegetative cells provided evidence for active actinomycete growth in marine sediments while indicating that a majority of sediment samples contained predominantly Salinispora spores at concentrations that could not be detected in environmental clone libraries. Challenges involved with the direct sequence-based detection of spore-forming microorganisms in environmental samples are discussed.

Mincer, TJ, Jensen PR, Kauffman CA, Fenical W.  2002.  Widespread and persistent populations of a major new marine actinomycete taxon in ocean sediments. Applied and Environmental Microbiology. 68:5005-5011.   10.1128/aem.68.10.5005-5011.2002   AbstractWebsite

A major taxon of obligate marine bacteria within the order Actinomycetales has been discovered from ocean sediments. Populations of these bacteria (designated MAR 1) are persistent and widespread, spanning at least three distinct ocean systems. In this study, 212 actinomycete isolates possessing MAR 1 morphologies were examined and all but two displayed an obligate requirement of seawater for growth. Forty-five of these isolates, representing all observed seawater-requiring morphotypes, were partially sequenced and found to share characteristic small-subunit rRNA signature nucleotides between positions 207 and 468 (Escherichia coli numbering). Phylogenetic characterization of seven representative isolates based on almost complete sequences of genes encoding 16S rRNA (16S ribosomal DNA) yielded a monophyletic clade within the family Micromonosporaceae and suggests novelty at the genus level. This is the first evidence for the existence of widespread populations of obligate marine actinomycetes. Organic extracts from cultured members of this new group exhibit remarkable biological activity, suggesting that they represent a prolific resource for biotechnological applications.

Miyanaga, A, Janso JE, McDonald L, He M, Liu HB, Barbieri L, Eustaquio AS, Fielding EN, Carter GT, Jensen PR, Feng XD, Leighton M, Koehn FE, Moore BS.  2011.  Discovery and Assembly-Line Biosynthesis of the Lymphostin Pyrroloquinoline Alkaloid Family of mTOR Inhibitors in Salinispora Bacteria. Journal of the American Chemical Society. 133:13311-13313.   10.1021/ja205655w   AbstractWebsite

The pyrroloquinoline alkaloid family of natural products, which includes the immunosuppressant lymphostin, has long been postulated to arise from tryptophan. We now report the molecular basis of lymphostin biosynthesis in three marine Salinispora species that maintain conserved biosynthetic gene clusters harboring a hybrid nonribosomal peptide synthetase-polyketide synthase that is central to lymphostin assembly. Through a series of experiments involving gene mutations, stable isotope profiling, and natural product discovery, we report the assembly-line biosynthesis of lymphostin and nine new analogues that exhibit potent mTOR inhibitory activity.

Moore, BS, Trischman JA, Seng D, Kho D, Jensen PR, Fenical W.  1999.  Salinamides, antiinflammatory depsipeptides from a marine streptomycete. Journal of Organic Chemistry. 64:1145-1150.   10.1021/jo9814391   AbstractWebsite

In addition to the previously reported antiinflammatory agents salinamides A and B from the marine isolate Streptomyces sp. CNB-091, three minor peptides are described. Their total structures were established using a combination of spectral and chemical techniques. Revised structures are presented for the bicyclic depsipeptides salinamides A and B on the basis of the analysis of the dansylated salinamide A hydrolysate by chiral capillary electrophoresis. The fermentation yield of salinamide D, which contains a D-valine residue in place of the D-isoleucine moiety in salinamide A, can be dramatically increased 30-fold by supplementing the growth media with L-valine. Salinamides C and E are monocyclic depsipeptides that are likely methylated byproducts of salinamide A biosynthetic intermediates.

Murphy, BT, Narender T, Kauffman CA, Woolery M, Jensen PR, Fenical W.  2010.  Saliniquinones A-F, New Members of the Highly Cytotoxic Anthraquinone-gamma-Pyrones from the Marine Actinomycete Salinispora arenicola. Australian Journal of Chemistry. 63:929-934.   10.1071/ch10068   AbstractWebsite

Six newanthraquinone-gamma-pyrones, saliniquinones A-F (1-6), which are related to metabolites of the pluramycin/altromycin class, were isolated from a fermentation broth of the marine actinomycete Salinispora arenicola (strain CNS-325). Their structures were determined by analysis of one-and two-dimensional NMR spectroscopic and high-resolution mass spectrometric data. The relative and absolute configurations of compounds 1-6 were determined by analysis of NOESY NMR spectroscopic data and by comparison of circular dichroism and optical rotation data with model compounds found in the literature. Saliniquinone A (1) exhibited potent inhibition of the human colon adenocarcinoma cell line (HCT-116) with an IC(50) of 9.9 x 10(-9) M. In the context of the biosynthetic diversity of S. arenicola, compounds 1-6 represent secondary metabolites that appear to be strain specific and thus occur outside of the core group of compounds commonly observed from this species.