William Fenical

William Fenical
University of California, San Diego | UCSD ·  Center for Marine Biotechnology and Biomedicine (CMBB)

PhD

About

783
Publications
64,294
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37,224
Citations
Additional affiliations
February 1973 - November 2015
University of California, San Diego
Position
  • Distinguished Professor of Oceanography and Pharmaceutical Science

Publications

Publications (783)
Article
HPLC-UV-guided fractionation of crude extract from the marine sediment-derived bacterium Streptomyces sp. CNP-944 has yielded two new pyrazine alkaloids, actinopolymorphols E and F (1 and 2), in addition to the previously reported biosynthetic product, actinopolymorphol G (3), and the known actinopolymorphol D (4). The chemical structures of 1−3 we...
Article
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The bioactive natural product seriniquinone was discovered as a potential melanoma drug, which was produced by the as-yet-undescribed marine bacterium of the rare genus Serinicoccus. As part of a long-term research program aimed at the discovery of new agents for the treatment of cancer, seriniquinone revealed remarkable in vitro activity against a...
Article
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Traditional cysticidal assays for Acanthamoeba species revolve around treating cysts with compounds and manually observing the culture for evidence of excystation. This method is time-consuming, labor-intensive, and low throughput. We adapted and trained a YOLOv3 machine learning, object detection neural network to recognize Acanthamoeba castellani...
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A new manumycin-type natural product named pacificamide (1) and its candidate biosynthetic gene cluster (pac) were discovered from the marine actinobacterium Salinispora pacifica CNT-855. The structure of the compound was determined using NMR, electronic circular dichroism, and bioinformatic predictions. The pac gene cluster is unique to S. pacific...
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The tricyclic quinazoline alkaloid deoxyvasicinone (DOV, 1) was isolated from a marine-derived Streptomyces sp. CNQ-617, and its anti-melanogenic effects were investigated. Deoxyvasicinone was shown to decrease the melanin content of B16F10 and MNT-1 cells that have been stimulated by α-melanocyte-stimulating hormone (α-MSH). In addition, microscop...
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A cyclic depsipeptide, nobilamide I (1), along with the known peptide A-3302-B/TL-119 (2), was isolated from the saline cultivation of the marine-derived bacterium Saccharomonospora sp., strain CNQ-490. The planar structure of 1 was elucidated by interpretation of 1D and 2D NMR and MS spectroscopic data. The absolute configurations of the amino aci...
Article
As part of a collaborative biomedical investigation of actinomycete bacteria isolated from sediments collected along the northern coast of Egypt (Mediterranean Sea), we explored the antibacterial metabolites from a bacterium identified as a Streptomyces sp., strain EG32. HPLC analysis and antibacterial testing against methicillin-resistant Staphylo...
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Analysis of the chemical components from the culture broth of the marine bacterium Saccharomonospora sp. CNQ-490 has yielded three novel compounds: saccharobisindole (1), neoasterric methyl ester (2), and 7-chloro-4(1H)-quinolone (3), in addition to acremonidine E (4), pinselin (5), penicitrinon A (6), and penicitrinon E (7). The chemical structure...
Article
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Isolated from the marine bacteria Serinicoccus sp., seriniquinone (SQ1) has been characterized by its selective activity in melanoma cell lines marked by its modulation of human dermcidin and induction of autophagy and apoptosis. While an active lead, the lack of solubility of SQ1 in both organic and aqueous media has complicated its preclinical ev...
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Four new chlorinated meroterpenoids, merochlorins G−J (1−4), and 10, a dihydronaphthalenedione precursor, along with known merochlorins A (5) and C−F (6−9), were obtained from cultivation of the bacterium strain Streptomyces sp. CNH-189, which was isolated from marine sediment. The planar structures of compounds 1−4 and 10 were elucidated by interp...
Article
Acremonamide (1) was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was established using MS, UV, and NMR spectroscopic data analyses. Acremonamide (1) was found to contain N-Me-Phe, N-Me-Ala, Val, Phe, and 2-hydroxyisovaleric acid. The absolute configurations of the four aforementioned amino ac...
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The chemical examination of two undescribed marine actinobacteria has yielded three rare merosesterterpenoids, marinoterpins A-C (1-3, respectively). These compounds were isolated from the culture broth extracts of two marine-derived actinomycetes associated with the family Streptomycetaceae, (our strains were CNQ-253 and AJS-327). The structures o...
Article
Ortho-quinone methides (o-QMs) are reactive intermediates in biosynthesis that give rise to a variety of intra- and intermolecular cyclization/addition products in bacteria, fungi, and plants. Herein, we report a new metabolic deviation of an o-QM intermediate in a benzylic dehydrogenation reaction that links the newly described marine bacterial na...
Article
We detail here distinctive departures from lead classical cholinesterase reactivators, the pyridinium aldoximes, to achieve rapid CNS penetration and reactivation of AChE in the CNS (brain and spinal cord). Such reactivation is consistent with these non‐canonical reactivators enhancing survival parameters in both mice and macaques following exposur...
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A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral meth...
Presentation
In addition to adequate pharmacological efficacy and safety profile, a balance of optimized bioavailability and reduced drug interactions potential maximizes the chance of a natural product becoming a successful therapy. Drug metabolism and pharmacokinetic (DMPK) screening must be evaluated firstly in vitro, which provides pharmacological orientati...
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A cyclic tetrapeptide, androsamide (1), was isolated from a marine actinomycete of the genus Nocardiopsis, strain CNT-189. The planar structure of 1 was assigned by the interpretation of 1D and 2D NMR spectroscopic data. The absolute configurations of constituent amino acids of 1 were determined by application of the Marfey's and advanced Marfey's...
Article
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A new linear type 1 polyketide, ionostatin (1) has been fully defined using a combined genomic and bioinformatics approach coupled with confirmatory chemical analyses. The 41 carbon-containing polyether is the product of the 101 kbp ion biosynthetic cluster containing seven modular type 1 polyketide synthases. Ionostatin is composed of 15 chiral ce...
Article
Seriniquinone is a secondary metabolite isolated from a rare marine bacterium of the genus Serinicoccus. This natural quinone is highlighted for its selective cytotoxic activity toward melanoma cancer cells, in which rapid metastatic properties are still a challenge for clinical treatment of malignant melanoma. The progress of seriniquinone as a pr...
Article
[3H]Diazonamide A ([3H]DZA), prepared from the natural product isolated from Diazona angulata, bound to tubulin in larger aberrant assembly products (>500 kDa by sizing HPLC) but not to the α,β-tubulin heterodimer. The binding reaction was rapid, but stoichiometry was low. Stoichiometry was enhanced up to 8-fold by preincubating the tubulin in the...
Article
The discovery of biologically active small molecules requires sifting through large amounts of data to identify unique or unusual arrangements of atoms. Here, we develop, test and evaluate an atom‐based sort to identify novel features of secondary metabolites and demonstrate its use to evaluate novelty in marine microbial and sponge extracts. This...
Article
Die Entdeckung biologisch aktiver Moleküle erfordert das Durchsuchen großer Datenmengen. Hier wird eine atombasierte Sortierung entwickelt, getestet und ausgewertet, um neue Eigenschaften von Sekundärmetaboliten zu identifizieren, was einen wichtigen Schritt hin zur Verwendung autonomer Systeme zur Identifizierung neuer Atomanordnungen innerhalb ei...
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Kozmin et al. contend that observations previously reported regarding the antimicrobial and antitumor activities of 6- N -hydroxy aminopurine (6-HAP) were incorrect. Their conclusions rely on poorly characterized reagents and focus strictly on in vitro techniques without validation in relevant mammalian model systems. We are pleased to be able to i...
Article
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Photopiperazines A-D (1-4), unsaturated diketopiperazine derivatives, were isolated from the culture broth of a rare, marine-derived actinomycete bacterium, strain AJS-327. This strain shows very poor 16S rRNA sequence similarity to other members of the actinomycete family Streptomycetaceae, indicating it is likely a new lineage within this group....
Article
Anti-renal cell carcinoma (RCC) agents with new mechanisms of action are urgently needed. Twenty seven natural products of the piericidin class, including seventeen new ones, are obtained from a marine-derived Streptomyces strain, and several of them show strong inhibitory activities against ACHN renal carcinoma cells. By exploring the mechanisms o...
Article
Meroterpenoids, meroindenon (1) and merochlorins E (2) and F (3), were isolated from a marine-derived bacterium belonging to the genus Streptomyces. Their chemical structures were established using extensive analysis of MS, UV, ECD, and NMR spectroscopic data. Compounds 1-3 possess a tetrahydroxynaphthalene core and a C15-isoprene unit. Compounds 2...
Article
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Analysis of the full genome of an environmentally-unique, halotolerant Streptomyces sp. strain GSL-6C, isolated from the Great Salt Lake, revealed a gene cluster encoding the biosynthesis of the salinipeptins, D-amino acid containing members of the rare linaridin subfamily of ribosomally synthesized and post-translationally modified peptides (RiPPs...
Article
Seriniquinone, a marine natural product, displayed potent cytotoxicity and selectivity against melanoma cancer cells. This selectivity, combined with a novel mode of action (MOA), prompted studies to translate a pharmacologically relevant lead. Herein, we report on structure-activity relationships (SARs), and provide a strategy to prepare analogues...
Article
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A cytotoxic alkaloidal meroterpenoid, saccharoquinoline (1), has been isolated from the fermentation broth of the marine-derived bacterium Saccharomonospora sp. CNQ-490. The planar structure of 1 was elucidated by 1D, 2D NMR, and MS spectroscopic data analyzes, while the relative configuration of 1 was defined through the interpretation of NOE spec...
Article
Full-text available
Seriniquinone is a natural quinone isolated from a rare marine bacterium of the genus Serinicoccus. This secondary metabolite has been shown to have anticancer properties, which has raised attention of the scientific community. In this short report, we present the first investigation of the gas-phase chemistry fragmentation reactions of seriniquino...
Article
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Contemporary sources of organohalogens produced as disinfection by-products (DBPs) are receiving considerable attention as emerging pollutants because of their abundance, persistence, and potential to structurally mimic natural organohalogens produced by bacteria that serve signaling and/or toxicological functions in marine environments. Here we te...
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A new 14-membered macrolactam natural product, fluvirucin B6 (1), was isolated from a marine-derived actinomycete, Nocardiopsis sp. CNQ-115, via HPLC-UV guided isolation. The chemical structure of 1 was elucidated by 1D and 2D NMR spectroscopic data analysis. Compound 1 showed a weak activity against Gram-positive bacteria, whereas it was inactive...
Article
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We report the discovery that strains of Staphylococcus epidermidis produce 6-N-hydroxyaminopurine (6-HAP), a molecule that inhibits DNA polymerase activity. In culture, 6-HAP selectively inhibited proliferation of tumor lines but did not inhibit primary keratinocytes. Resistance to 6-HAP was associated with the expression of mitochondrial amidoxime...
Chapter
Marine bacteria are beginning to occupy a central role in the discovery of new bioactive molecules. The diversity of marine microbial habitats, each with its unique environmental traits and characteristic dominance of certain bacterial Phyla, are described herein. Sampling strategies for deep-sea marine sediments, as well as isolation methods are d...
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Bacterial natural products remain an important source of new medicines. DNA sequencing has revealed that a majority of natural product biosynthetic gene clusters (BGCs) maintained in bacterial genomes have yet to be linked to the small molecules whose biosynthesis they encode. Efforts to discover the products of these orphan BGCs are driving the de...
Article
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Intensive study of the organic extract of the marine-derived bacterium Saccharomonospora sp. CNQ-490 has yielded three new α-pyrones, saccharomonopyrones A–C (1–3). The chemical structures of these compounds were assigned from the interpretation of 1D, 2D NMR and mass spectrometry data. Saccharomonopyrone A (1) is the first α-pyrone microbial natur...
Article
HPLC-UV guided isolation of the culture broth of a marine bacterium Saccharomonospora sp. CNQ-490 has led to the isolation of two new natural products, lodopyridones B and C (1 and 2) along with the previously reported lodopyridone A (3). Their chemical structures were established from the interpretation of 2D NMR spectroscopic data and the compari...
Article
HPLC-UV guided isolation for the culture broth extract of the marine-derived bacterium Streptomyces sp. has led to the two 14-membered macrolides, 4Z- (1) and 4E-12-dehydroxykromycins (2). The chemical structures of compounds 1 and 2 were elucidated by spectral data, while the absolute stereochemistry of 1 and 2 were determined by application of ci...
Article
Two piloquinone derivatives isolated from Streptomyces sp. CNQ-027 were tested for the inhibitory activities of two isoforms of monoamine oxidase (MAO), which catalyzes monoamine neurotransmitters. The piloquinone 4,7-dihydroxy-3-methyl-2-(4-methyl-1-oxopentyl)-6H-dibenzo[b,d]pyran-6-one (1) was found to be a highly potent inhibitor of human MAO-B,...
Article
Polyhalogenated N-methylbi- pyrroles of two different structure classes have been detected worldwide in over 100 environmental samples including seawater, bird eggs, fish, dolphin blubber, and in the breast milk of humans that consume seafood. These molecules are concentrated in the fatty tissues in comparable abundance to some of the most importan...
Article
Vibrio cholerae is the causative bacteria of the diarrheal disease cholera, but also persists in aquatic environments where it displays an expression profile that is distinct from that during infection. Upon entry into the host, a tightly regulated circuit coordinates induction of two major virulence factors: cholera toxin (CT) and a toxin co-regul...
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Understanding trafficking in cells and tissues is one of the most critical steps in exploring the mechanisms and modes of action (MOAs) of a small molecule. Typically, deciphering the role of concentration presents one of the most difficult challenges associated with this task. Herein, we present a practical solution to this problem by developing c...
Article
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Understanding the target and mode of action (MOA) of small molecules activity has become a critical feature in guiding the transition between drug discovery and clinical evaluation. While classically placed at the latter stages of a discovery program, we now describe how addressing the mode of action of natural products at the early stages of a pro...
Article
Ansalactams B—D exhibit weak antibacterial activity against methicillin-resistant S.aureus (MRSA).
Article
The piericidin family of microbial metabolites features a 4-pyridinol core linked with a methylated polyketide side chain. Piericidins are exclusively produced by actinomycetes, especially members of the genus Streptomyces. The close structural similarity with coenzyme Q renders the piericidins important NADH-ubiquinone oxidoreductase (complex I) i...
Article
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Actinomycete bacteria of the common genus Streptomyces can be routinely isolated from shallow and deep ocean sediments. Although commonly considered a terrestrial genus, and most abundantly found in soil, Streptomyces strains are found that have distinct requirements for seawater and routinely do not show significant similarity, with terrestrial st...
Article
Further chemical investigation of a marine-derived bacterium of the genus Streptomyces has led to the isolation of ansalactams B-D (1-3) along with the previously reported metabolite ansalactam A (4). Ansalactams B-D are significantly modified ansamycins, representing three new carbon skeletons and further illustrating the biosynthetic plasticity o...
Article
Two actinomycetes, a member of the rare halophilic genus Streptomonospora and a Nocardiopsis sp. (Nocardiopsaceae), strains CNQ-082 and CNQ-675, respectively, were isolated from marine sediments collected off shore near La Jolla, California. HPLC-UV guided fractionations of the extracts of these strains yielded marinopyrones A–D (1–4), the structur...
Article
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Chemical investigation of a marine-derived actinomycete isolated from marine sediments collected off the coast of southern California and identified as a Nocardiopsis sp. (strain CNQ115) led to the isolation of two new 4-aminoimidazole alkaloids, nocarimidazoles A (1) and B (2). The chemical structures of nocarimidazoles A and B were assigned by in...
Article
Chlorotonil A is a novel polyketide isolated from the myxobacterium Sorangium cellulosum So ce1525 that features a unique gem-dichloro-1,3-dione moiety. It exhibits potent bioactivity, most notably against the problematic malaria pathogen Plasmodium falciparum in the nanomolar range. In addition, strong antibacterial and moderate antifungal activit...
Article
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Sponges of the genus Aplysina are among the most common benthic animals on reefs of the Caribbean, and display a wide diversity of morphologies and colors. Tissues of these sponges lack mineralized skeletal elements, but contain a dense spongin skeleton and an elaborate series of tyrosine-derived brominated alkaloid metabolites that function as che...
Article
Streptomyces sp. CNQ-509 is a marine actinomycete belonging to the MAR4 streptomycete lineage. MAR4 strains have been linked to the production of diverse and otherwise rare meroterpenoid compounds. The genome sequence of Streptomyces sp. CNQ-509 was found to contain 29 putative gene clusters for the biosynthesis of secondary metabolites, some of th...
Article
Low-nutrient media and long incubation times facilitated the cultivation of 20 taxonomically diverse Gram-negative marine bacteria within the phyla Bacteroidetes and Proteobacteria. These strains comprise as many as three new families and include members of clades that had only been observed using culture-independent techniques. Chemical studies of...