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Recent Publications

  • Tang X.Y, Kudo Y., Baker J.L, LaBonte S., Jordan P.A, McKinnie S.MK, Guo J., Huan T., Moore BS, Edlund A..  2020.  Cariogenic Streptococcus mutans produces tetramic acid strain-specific antibiotics that impair commensal colonization. 6:563-571.
    Abstract Summary:

    Streptococcus mutans is a common constituent of dental plaque and a major etiologic agent of dental caries (tooth decay). In this study, we elucidated the biosynthetic pathway encoded by muc, a hybrid polyketide synthase and nonribosomal peptide synthetase (PKS/NRPS) biosynthetic gene cluster (BGC), present in a number of globally distributed S. mutans strains. The natural products synthesized by muc included three N-acyl tetramic acid...

  • Hindell M.A, Reisinger R.R, Ropert-Coudert Y., Huckstadt L.A, Trathan P.N, Bornemann H., Charrassin J.B, Chown S.L, Costa D.P, Danis B. et al..  2020.  Tracking of marine predators to protect Southern Ocean ecosystems.
    Abstract Summary:

    Tracking data from 17 marine predator species in the Southern Ocean are used to identify Areas of Ecological Significance, the protection of which could help to mitigate increasing pressures on Southern Ocean ecosystems. Southern Ocean ecosystems are under pressure from resource exploitation and climate change(1,2). Mitigation requires the identification and protection of Areas of Ecological Significance (AESs), which have so far not been...

  • Reher R., Kim H.W, Zhang C., Mao H.H, Wang M.X, Nothias L.F, Caraballo-Rodriguez A.M, Glukhov E., Teke B., Leao T. et al..  2020.  A convolutional neural network-based approach for the rapid annotation of molecularly diverse natural products. 142:4114-4120.
    Abstract Summary:

    This report describes the first application of the novel NMR-based machine learning tool "Small Molecule Accurate Recognition Technology" (SMART 2.0) for mixture analysis and subsequent accelerated discovery and characterization of new natural products. The concept was applied to the extract of a filamentous marine cyanobacterium known to be a prolific producer of cytotoxic natural products. This environmental Symploca extract was roughly...

  • Liu S, Ahmed S., Zhang C.G, Liu T.X, Shao C.L, Fang Y.W.  2020.  Diversity and antimicrobial activity of culturable fungi associated with sea anemone Anthopleura xanthogrammica. 44:41-46.
    Abstract Summary:

    Background: The main objective of this study was to isolate fungi associated with Anthopleura xanthogrammica and measure their antimicrobial and enzymatic activities. A total of 93 fungal strains associated with A. xanthogrammica were isolated in this study, of which 32 isolates were identified using both morphological characteristics and internal transcribed spacer (ITS) sequence analysis. The antibacterial activities of 32 fungal isolates...

  • Ropert-Coudert Y., Van de Putte A.P, Reisinger R.R, Bornemann H., Charrassin J.B, Costa D.P, Danis B., Huckstadt L.A, Jonsen I.D, Lea M.A et al..  2020.  The retrospective analysis of Antarctic tracking data project. 7
    Abstract Summary:

    The Retrospective Analysis of Antarctic Tracking Data (RAATD) is a Scientific Committee for Antarctic Research project led jointly by the Expert Groups on Birds and Marine Mammals and Antarctic Biodiversity Informatics, and endorsed by the Commission for the Conservation of Antarctic Marine Living Resources. RAATD consolidated tracking data for multiple species of Antarctic meso- and top-predators to identify Areas of Ecological Significance...

  • Fiore M.F, de Lima S.T, Carmichael W.W, McKinnie S.MK, Chekan J.R, Moore BS.  2020.  Guanitoxin, re-naming a cyanobacterial organophosphate toxin. 92
    Abstract Summary:

    Anatoxin-a(S) is the most potent natural neurotoxin produced by fresh water cyanobacteria. It is also the least understood and monitored. Although this potent cholinesterase inhibitor was first reported in the 1970s and connected with animal poisonings, the lack of chemical standards and identified biosynthetic genes together with limited diagnostics and acute reactivity of this naturally-occurring organophosphate have limited our...

  • Bai R., Cruz-Monserrate Z., Fenical W, Pettit G.R, Hamel E..  2020.  Interaction of diazonamide A with tubulin. 680
    Abstract Summary:

    [H-3]Diazonamide A ([H-3]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 alpha beta-tubulin heterodimer. The binding reaction was rapid, but stoichiometry was low. Stoichiometry was enhanced up to 8-fold by preincubating the tubulin in the reaction mixture prior to adding the [H-3]DZA. Although Mg2+ did not affect binding...

  • Yi J.S, Yoo H.W, Kim E.J, Yang Y.H, Kim B.G.  2020.  Engineering Streptomyces coelicolor for production of monomethyl branched chain fatty acids. 307:69-76.
    Abstract Summary:

    Branched chain fatty acids (BCFA) are an appealing biorefinery-driven target of fatty acid (FA) production. BCFAs typically have lower melting points compared to straight chain FAs, making them useful in lubricants and biofuels. Actinobacteria, especially Streptomyces species, have unique secondary metabolism that are capable of producing not only antibiotics, but also high percentage of BCFAs in their membrane lipids. Since biosynthesis of...

  • Zhang J.J, Tang X.Y, Huan T., Ross AC, Moore BS.  2020.  Pass-back chain extension expands multimodular assembly line biosynthesis. 16:42-+.
    Abstract Summary:

    Modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymatic assembly lines are large and dynamic protein machines that generally effect a linear sequence of catalytic cycles. Here, we report the heterologous reconstitution and comprehensive characterization of two hybrid NRPS-PKS assembly lines that defy many standard rules of assembly line biosynthesis to generate a large combinatorial library of cyclic...

  • Skiba M.A, Tran C.L, Dan Q.Y, Sikkema A.P, Klaver Z., Gerwick WH, Sherman D.H, Smith J.L.  2020.  Repurposing the GNAT fold in the initiation of polyketide biosynthesis. 28:63-+.
    Abstract Summary:

    Natural product biosynthetic pathways are replete with enzymes repurposed for new catalytic functions. In some modular polyketide synthase (PKS) pathways, a GCN5-related N-acetyltransferase (GNAT)-like enzyme with an additional decarboxylation function initiates biosynthesis. Here, we probe two PKS GNAT-like domains for the dual activities of S-acyl transfer from coenzyme A (CoA) to an acyl carrier protein (ACP) and decarboxylation. The GphF...

  • Gauglitz J.M, Aceves C.M, Aksenov A.A, Aleti G., Almaliti J., Bouslimani A., Brown E.A, Campeau A., Caraballo-Rodriguez A.M, Chaar R. et al..  2020.  Untargeted mass spectrometry-based metabolomics approach unveils molecular changes in raw and processed foods and beverages. 302
    Abstract Summary:

    In our daily lives, we consume foods that have been transported, stored, prepared, cooked, or otherwise processed by ourselves or others. Food storage and preparation have drastic effects on the chemical composition of foods. Untargeted mass spectrometry analysis of food samples has the potential to increase our chemical understanding of these processes by detecting a broad spectrum of chemicals. We performed a time-based analysis of the...

  • Chekan J.R, Lee G.Y, A. Gamal E, Purdy T.N, Houk K.N, Moore BS.  2019.  Bacterial tetrabromopyrrole debrominase shares a reductive dehalogenation strategy with human thyroid deiodinase. 58:5329-5338.
    Abstract Summary:

    Enzymatic dehalogenation is an important and well-studied biological process in both the detoxification and catabolism of small molecules, many of which are anthro-pogenic in origin. However, dedicated dehalogenation reactions that replace a halogen atom with a hydrogen are rare in the biosynthesis of natural products. In fact, the debrominase Bmp8 is the only known example. It catalyzes the reductive debromination of the coral settlement cue...

  • Goldbogen J.A, Cade D.E, Calambokidis J, Czapanskiy M.F, Fahlbusch J., Friedlaender A.S, Gough W.T, Kahane-Rapport S.R, Savoca M.S, Ponganis K.V et al..  2019.  Extreme bradycardia and tachycardia in the world's largest animal. 116:25329-25332.
    Abstract Summary:

    The biology of the blue whale has long fascinated physiologists because of the animal's extreme size. Despite high energetic demands from a large body, low mass-specific metabolic rates are likely powered by low heart rates. Diving bradycardia should slow blood oxygen depletion and enhance dive time available for foraging at depth. However, blue whales exhibit a high-cost feeding mechanism, lunge feeding, whereby large volumes of prey-laden...

  • Morandini V., Dugger K.M, Ballard G., Elrod M., Schmidt A., Ruoppolo V., Lescroel A., Jongsomjit D., Massaro M., Pennycook J. et al..  2019.  Identification of a novel Adelie penguin circovirus at Cape Crozier (Ross Island, Antarctica). 11
    Abstract Summary:

    Understanding the causes of disease in Antarctic wildlife is crucial, as many of these species are already threatened by environmental changes brought about by climate change. In recent years, Antarctic penguins have been showing signs of an unknown pathology: a feather disorder characterised by missing feathers, resulting in exposed skin. During the 2018-2019 austral summer breeding season at Cape Crozier colony on Ross Island, Antarctica,...

  • Cao L., Gurevich A., Alexander K.L, Naman C.B, Leao T., Glukhov E., Luzzatto-Knaan T., Vargas F., Quinn R., Bouslimani A. et al..  2019.  MetaMiner: A scalable peptidogenomics approach for discovery of ribosomal peptide natural products with blind modifications from microbial communities. 9:600-+.
    Abstract Summary:

    Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an important class of natural products that contain antibiotics and a variety of other bioactive compounds. The existing methods for discovery of RiPPs by combining genome mining and computational mass spectrometry are limited to discovering specific classes of RiPPs from small datasets, and these methods fail to handle unknown post-translational modifications....

  • Klasek S., Torres M.E, Bartlett DH, Tyler M., Hong W.L, Colwell F..  2019.  Microbial communities from Arctic marine sediments respond slowly to methane addition during ex situ enrichments.
    Abstract Summary:

    Anaerobic methanotrophic archaea (ANME) consume methane in marine sediments, limiting its release to the water column, but their responses to changes in methane and sulfate supplies remain poorly constrained. To address how methane exposure may affect microbial communities and methane- and sulfur-cycling gene abundances in Arctic marine sediments, we collected sediments from offshore Svalbard that represent geochemical horizons where...

  • Huang L.M, Ding L.J, Li X.H, Wang N., Cui W., Wang X., Naman C.B, Lazaro J.EH, Van X.J, He S..  2019.  New dihydroisocoumarin root growth inhibitors from the sponge-derived fungus Aspergillus sp. NBUF87. 10
    Abstract Summary:

    Six new dihydroisocoumarins, aspergimarins A-F (1-6), were discovered together with five known analogs (7-11) from a monoculture of the sponge-derived fungus Aspergillus sp. NBUF87. The structures of these compounds were elucidated through comprehensive spectroscopic methods, and absolute configurations were assigned after X-ray crystallography, use of the modified Mosher's method, and comparison of electronic circular dichroism (ECD) data...

  • Rajput A., Poudel S., Tsunemoto H., Meehan M., Szubin R., Olson C.A, Lamsa A., Seif Y., Dillon N., Vrbanac A. et al..  2019.  Profiling the effect of nafcillin on HA-MRSA D712 using bacteriological and physiological media. 6
    Abstract Summary:

    Staphylococcus aureus strains have been continuously evolving resistance to numerous classes of antibiotics including methicillin, vancomycin, daptomycin and linezolid, compounding the enormous healthcare and economic burden of the pathogen. Cation-adjusted Mueller-Hinton broth (CA-MHB) is the standard bacteriological media for measuring antibiotic susceptibility in the clinical lab, but the use of media that more closely mimic the...

  • O'Donoghue A.J, Bibo-Verdugo B., Miyamoto Y., Wang S.C, Yang J.Z, Zuill D.E, Matsuka S., Jiang Z.Z, Almaliti J., Caffrey C.R et al..  2019.  20S proteasome as a drug target in Trichomonas vaginalis. 63
    Abstract Summary:

    Trichomoniasis is a sexually transmitted disease with hundreds of millions of annual cases worldwide. Approved treatment options are limited to two related nitro-heterocyclic compounds, yet resistance to these drugs is an increasing concern. New antimicrobials against the causative agent, Trichomonas vaginalis, are urgently needed. We show here that clinically approved anticancer drugs that inhibit the proteasome, a large protease complex...

  • Meijers A.JS, Cerovecki I, King B.A, Tamsitt V..  2019.  A see-saw in Pacific subantarctic mode water formation driven by atmospheric modes.
    Abstract Summary:

    Subantarctic Mode Water (SAMW) in the Pacific forms in two distinct pools in the south central and southeast Pacific, which subduct into the ocean interior and impact global storage of heat and carbon. Wintertime thickness of the central and eastern SAMW pools vary predominantly out of phase with each other, by up to +/- 150 m between years, resulting in an interannual thickness see-saw. The thickness in the eastern (central) pool is found to...

  • Abstract Summary:

    In response to environmental change, organisms rely on both genetic adaptation and phenotypic plasticity to adjust key traits that are necessary for survival and reproduction. Given the accelerating rate of climate change, plasticity may be particularly important. For organisms in warming aquatic habitats, upper thermal tolerance is likely to be a key trait, and many organisms express plasticity in this trait in response to developmental or...

  • Boudreau P.D, Miller B.W, McCall L.I, Almaliti J., Reher R., Hirata K., Le T., Siqueira-Neto J.L, Hook V., Gerwick WH.  2019.  Design of Gallinamide A analogs as potent inhibitors of the cysteine proteases human Cathepsin L and Trypanosoma cruzi Cruzain. 62:9026-9044.
    Abstract Summary:

    Gallinamide A, originally isolated with a modest antimalarial activity, was subsequently reisolated and characterized as a potent, selective, and irreversible inhibitor of the human cysteine protease cathepsin L. Molecular docking identified potential modifications to improve binding, which were synthesized as a suite of analogs. Resultingly, this current study produced the most potent gallinamide analog yet tested against cathepsin L (10, K-...

  • Eiben C.B, de Rond T., Bloszies C., Gin J., Chiniquy J., Baidoo E.EK, Petzold C.J, Hillson N.J, Fiehn O., Keasling J.D.  2019.  Mevalonate pathway promiscuity enables noncanonical terpene production. 8:2238-2247.
    Abstract Summary:

    Lepidoptera (butterflies and moths) make the six-carbon compounds homoisopentenyl pyrophosphate (HIPP) and homodimethylallyl pyrophosphate (HDMAPP) that are incorporated into 16, 17, and 18 carbon farnesyl pyrophosphate (FPP) analogues. In this work we heterologously expressed the lepidopteran modified mevalonate pathway, a propionyl-CoA ligase, and terpene cyclases in E. coli to produce several novel terpenes containing 16 carbons. Changing...

  • Ding Y., Murphy K.M, Poretsky E., Mafu S., Yang B, Char S.N, Christensen S.A, Saldivar E., Wu M.X, Wang Q. et al..  2019.  Multiple genes recruited from hormone pathways partition maize diterpenoid defences. 5:1043-1056.
    Abstract Summary:

    Duplication and divergence of primary pathway genes underlie the evolution of plant specialized metabolism; however, mechanisms partitioning parallel hormone and defence pathways are often speculative. For example, the primary pathway intermediate ent-kaurene is essential for gibberellin biosynthesis and is also a proposed precursor for maize antibiotics. By integrating transcriptional coregulation patterns, genome-wide association studies,...

  • Abstract Summary:

    The new phthalideisoquinoline hemiacetal alkaloids (2-7) and the known analogues (1 and 8) were isolated from the bulbs of Corydalis decumbens. The new compounds were characterized by analysis of their NMR spectroscopic data, chemical degradation syntheses, X-ray crystallography, and comparison of experimental and calculated ECD data. All the isolates were screened in vitro for inhibitory activity of spontaneous calcium oscillations in...

  • Bibo-Verdugo B., Wang S.C, Almaliti J., Ta A.P, Jiang Z.Z, Wong D.A, Lietz C.B, Suzuki B.M, El-Saldary N., Hook V. et al..  2019.  The proteasome as a drug target in the metazoan pathogen, Schistosoma mansoni. 5:1802-1812.
    Abstract Summary:

    Proteases are fundamental to successful parasitism, including that of the schistosome flatworm parasite, which causes the disease schistosomiasis in 200 million people worldwide. The proteasome is receiving attention as a potential drug target for treatment of a variety of infectious parasitic diseases, but it has been understudied in the schistosome. Adult Schistosoma mansoni were incubated with 1 mu M concentrations of the proteasome...

  • Duggan BM, Cullum R., Fenical W, Amador L.A, Rodriguez A.D, La Clair J.J.  2019.  Searching for small molecules with an atomic sort.
    Abstract Summary:

    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 study outlines an important ongoing advance towards the translation of autonomous systems to...

  • Tietze D., Kaufmann D., Tietze A.A, Vo A., Reher R., Konig G., Hausch F..  2019.  Structural and dynamical basis of G protein inhibition by YM-254890 and FR900359: An inhibitor in action. 59:4361-4373.
    Abstract Summary:

    Specific inhibition of G proteins holds a great pharmacological promise to, e.g., target oncogenic G(q/11) proteins and can be achieved by the two natural products FR900359 (FR) and YM-254890 (YM). Unfortunately, recent rational-design-based approaches to address G proteins other than G(q/11/14) subtypes were not successful mainly due to the conformational complexity of these new modalities-like compounds. Here, we report the water-derived...

  • Yu H.B, Glukhov E., Li Y.Y, Iwasaki A., Gerwick L, Dorrestein PC, Jiao B.H, Gerwick WH.  2019.  Cytotoxic microcolin lipopeptides from the marine cyanobacterium Moorea producens. 82:2608-2619.
    Abstract Summary:

    Nine new linear lipopeptides, microcolins E-M (1-9), together with four known related compounds, microcolins A-D (10-13), were isolated from the marine cyanobacterium Moorea producens using bioassay-guided and LC-MS/MS molecular networking approaches. Catalytic hydrogenation of microcolins A-D (10-13) yielded two known compounds, 3,4-dihydromicrocolins A and B (14, 15), and two new derivatives, 3,4-dihydromicrocolins C and D (16, 17),...

  • Zhang J.J, Tang X.Y, Moore BS.  2019.  Genetic platforms for heterologous expression of microbial natural products. 36:1313-1332.
    Abstract Summary:

    Covering: 2005 up to 2019 Natural products are of paramount importance in human medicine. Not only are most antibacterial and anticancer drugs derived directly from or inspired by natural products, many other branches of medicine, such as immunology, neurology, and cardiology, have similarly benefited from natural product-based drugs. Typically, the genetic material required to synthesize a microbial specialized product is arranged in a...

  • Chase A.B, Arevalo P., Brodie E.L, Polz M.F, Karaoz U., Martiny J.BH.  2019.  Maintenance of sympatric and allopatric populations in free-living terrestrial bacteria. 10
    Abstract Summary:

    For free-living bacteria and archaea, the equivalent of the biological species concept does not exist, creating several obstacles to the study of the processes contributing to microbial diversification. These obstacles are particularly high in soil, where high bacterial diversity inhibits the study of closely related genotypes and therefore the factors structuring microbial populations. Here, we isolated strains within a single Curtobacterium...

  • Li T., Wang N., Zhang T., Zhang B., Sajeevan T.P, Joseph V., Armstrong L., He S., Yan X.J, Naman C.B.  2019.  A systematic review of recently reported marine derived natural product kinase inhibitors. 17
    Abstract Summary:

    Protein kinases are validated drug targets for a number of therapeutic areas, as kinase deregulation is known to play an essential role in many disease states. Many investigated protein kinase inhibitors are natural product small molecules or their derivatives. Many marine-derived natural products from various marine sources, such as bacteria and cyanobacteria, fungi, animals, algae, soft corals, sponges, etc. have been found to have potent...

  • Zhou X.F, Liang Z., Li K.L, Fang W., Tian Y.X, Luo X.W, Chen Y.L, Zhan Z.K, Zhang T., Liao S.R et al..  2019.  Exploring the natural piericidins as anti-renal cell carcinoma agents targeting peroxiredoxin 1. 62:7058-7069.
    Abstract Summary:

    Anti-renal cell carcinoma (RCC) agents with new mechanisms of action are urgently needed. Twenty-seven natural products of the piericidin class, including 17 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 of two representative natural piericidin compounds, piericidin A (PA) and glucopiericidin A (GPA),...

  • Ryu M.J, Hwang S., Kim S, Yang I., Oh D.C, Nam SJ, Fenical W.  2019.  Meroindenon and merochlorins E and F, antibacterial meroterpenoids from a marine-derived sediment bacterium of the genus Streptomyces. 21:5779-5783.
    Abstract Summary:

    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 C-15-isoprene unit. Compounds 2 and 3 exhibited strong antibacterial activities against B. subtilis, K. rhizophila, and S....

  • Valiadi M., de Rond T., Amorim A., Gittins J.R, Gubili C., Moore BS, Iglesias-Rodriguez M.D, Latz M.I.  2019.  Molecular and biochemical basis for the loss of bioluminescence in the dinoflagellate Noctiluca scintillans along the west coast of the USA.
    Abstract Summary:

    The globally distributed heterotrophic dinoflagellate Noctiluca scintillans (Macartney) Kofoid & Swezy is well known for its dense blooms and prominent displays of bioluminescence. Intriguingly, along the west coast of the U.S.A., its blooms are not bioluminescent. We investigated the basis for this regional loss of bioluminescence using molecular, cellular, and biochemical analyses of isolates from different geographic regions. Several...

  • Abstract Summary:

    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. The structures of the photopiperazines were defined by analysis of HR-ESI-TOF-MS spectra in...

  • de Rond T., Gao J., Zargar A., de Raad M., Cunha J., Northen T.R, Keasling J.D.  2019.  A high-throughput mass spectrometric enzyme activity assay enabling the discovery of cytochrome P450 biocatalysts. 58:10114-10119.
    Abstract Summary:

    Assaying for enzymatic activity is a persistent bottleneck in biocatalyst and drug development. Existing high-throughput assays for enzyme activity tend to be applicable only to a narrow range of biochemical transformations, whereas universal enzyme characterization methods usually require chromatography to determine substrate turnover, greatly diminishing throughput. We present an enzyme activity assay that allows the high-throughput mass-...

  • Moss N.A, Seiler G., Leao T.F, Castro-Falcon G., Gerwick L, Hughes CC, Gerwick WH.  2019.  Nature's combinatorial biosynthesis produces vatiamides A-F. 58:9027-9031.
    Abstract Summary:

    Hybrid typeI PKS/NRPS biosynthetic pathways typically proceed in a collinear manner wherein one molecular building block is enzymatically incorporated in a sequence that corresponds to gene arrangement. In this work, genome mining combined with the use of a fluorogenic azide-based click probe led to the discovery and characterization of vatiamides A-F, three structurally diverse alkynylated lipopeptides, and their brominated analogues, from...

  • Abstract Summary:

    The lymphostins are a family of closely related pyrrolo[4,3,2-de]quinoline natural products produced by Streptomyces and Salinispora actinobacteria. Neolymphostin A was recently shown to strongly inhibit phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) in a covalent manner via conjugation to a catalytic lysine residue in the ATP-binding pocket of the enzymes, making this metabolite the first reported covalent...

  • Luhavaya H., Sigrist R., Chekan J.R, McKinnie S.MK, Moore BS.  2019.  Biosynthesis of l-4-chlorokynurenine, an antidepressant prodrug and a non-proteinogenic amino acid found in lipopeptide antibiotics. 58:8394-8399.
    Abstract Summary:

    l-4-Chlorokynurenine (l-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder. Recently, this amino acid was naturally found as a residue in the lipopeptide antibiotic taromycin. Herein, we report the unprecedented conversion of l-tryptophan into l-4-Cl-Kyn catalyzed by four enzymes in the taromycin biosynthetic pathway from the marine bacterium Saccharomonospora sp. CNQ-490....

  • Schorn MA, Jordan PA, Podell S, Blanton JM, Agarwal V, Biggs JS, Allen EE, Moore BS.  2019.  Comparative genomics of cyanobacterial symbionts reveals distinct, specialized metabolism in tropical Dysideidae sponges. 10
    Abstract Summary:

    Marine sponges are recognized as valuable sources of bioactive metabolites and renowned as petri dishes of the sea, providing specialized niches for many symbiotic microorganisms. Sponges of the family Dysideidae are well documented to be chemically talented, often containing high levels of polyhalogenated compounds, terpenoids, peptides, and other classes of bioactive small molecules. This group of tropical sponges hosts a high abundance of...

  • Chekan J.R, McKinnie S.MK, Moore M.L, Poplawski S.G, Michael T.P, Moore BS.  2019.  Scalable biosynthesis of the seaweed neurochemical, kainic acid. 58:8454-8457.
    Abstract Summary:

    Kainic acid, the flagship member of the kainoid family of natural neurochemicals, is a widely used neuropharmacological agent that helped unravel the key role of ionotropic glutamate receptors, including the kainate receptor, in the central nervous system. Worldwide shortages of this seaweed natural product in the year 2000 prompted numerous chemical syntheses, including scalable preparations with as few as six-steps. Herein we report the...

  • Busch J., Agarwal V., Schorn M., Machado H., Moore BS, Rouse GW, Gram L., Jensen PR.  2019.  Diversity and distribution of the bmp gene cluster and its Polybrominated products in the genus Pseudoalteromonas. 21:1575-1585.
    Abstract Summary:

    The production of pentabromopseudilin and related brominated compounds by Pseudoalteromonas spp. has recently been linked to the bmp biosynthetic gene cluster. This study explored the distribution and evolutionary history of this gene cluster in the genus Pseudoalteromonas. A phylogeny of the genus revealed numerous clades that do not contain type strains, suggesting considerable species level diversity has yet to be described. Comparative...

  • Walsh CT, Moore BS.  2019.  Enzymatic cascade reactions in biosynthesis. 58:6846-6879.
    Abstract Summary:

    Enzyme-mediated cascade reactions are widespread in biosynthesis. To facilitate comparison with the mechanistic categorizations of cascade reactions by synthetic chemists and delineate the common underlying chemistry, we discuss four types of enzymatic cascade reactions: those involving nucleophilic, electrophilic, pericyclic, and radical reactions. Two subtypes of enzymes that generate radical cascades exist at opposite ends of the oxygen...

  • Carvajal M., Araya-Cornejo C., Sepulveda I., Melnick D., Haase JS.  2019.  Nearly instantaneous tsunamis following the Mw 7.5 2018 Palu earthquake. 46:5117-5126.
    Abstract Summary:

    The tsunami observations produced by the 2018 magnitude 7.5 Palu strike-slip earthquake challenged the traditional basis underlying tsunami hazard assessments and early warning systems. We analyzed an extraordinary collection of 38 amateur and closed circuit television videos to show that the Palu tsunamis devastated widely separated coastal areas around Palu Bay within a few minutes after the mainshock and included wave periods shorter than...

  • Bauman K.D, Li J., Murata K., Mantovani S.M, Dahesh S., Nizet V., Luhavaya H., Moore BS.  2019.  Refactoring the cryptic streptophenazine biosynthetic gene cluster unites phenazine, polyketide, and nonribosomal peptide biochemistry. 26:724-+.
    Abstract Summary:

    The disconnect between the genomic prediction of secondary metabolite biosynthetic potential and the observed laboratory production profile of microorganisms is well documented. While heterologous expression of biosynthetic gene clusters (BGCs) is often seen as a potential solution to bridge this gap, it is not immune to many challenges including impaired regulation, the inability to recruit essential building blocks, and transcriptional and/...

  • Abstract Summary:

    Anatomical and physiological adaptations of animals to extreme environments provide insight into basic physiological principles and potential therapies for human disease. In that regard, the diving physiology of marine mammals and seabirds is especially relevant to pulmonary and cardiovascular function, and to the pathology and potential treatment of patients with hypoxaemia and/or ischaemia. This review highlights past and recent progress in...

  • Williams C.L, Sato K., Ponganis P.J.  2019.  Activity, not submergence, explains diving heart rates of captive loggerhead sea turtles. Journal of Experimental Biology. 222
    Abstract Summary:

    Marine turtles spend their life at sea and can rest on the seafloor for hours. As air-breathers, the breath-hold capacity of marine turtles is a function of oxygen (O-2) stores, O-2 consumption during dives and hypoxia tolerance. However, some physiological adaptations to diving observed in mammals are absent in marine turtles. This study examined cardiovascular responses in loggerhead sea turtles, which have even fewer adaptations to diving...

  • Tayler N.M, Boya C.A, Herrera L., Moy J., Ng M., Pineda L., Almanza A., Rosero S., Coronado L.M, Correa R. et al..  2019.  Analysis of the antiparasitic and anticancer activity of the coconut palm (Cocos nucifera L. ARECACEAE) from the natural reserve of Punta Patino, Darien. Plos One. 14
    Abstract Summary:

    Cocos nucifera (C. nucifera) (the coconut palm tree) has been traditionally used to fight a number of human diseases, but only a few studies have tested its components against parasites such as those that cause malaria. In this study, C. nucifera samples were collected from a private natural reserve in Punta Patino, Darien, Panama. The husk, leaves, pulp, and milk of C. nucifera were extracted and evaluated against the parasites that cause...

  • Poudel S., Tsunemoto H., Meehan M., Szubin R., Olson C.A, Lamsa A., Seif Y., Dillon N., Vrbanac A., Sugie J. et al..  2019.  Characterization of CA-MRSA TCH1516 exposed to nafcillin in bacteriological and physiological media. Scientific Data. 6
    Abstract Summary:

    Cation adjusted-Mueller Hinton Broth (CA-MHB) is the standard bacteriological medium utilized in the clinic for the determination of antibiotic susceptibility. However, a growing number of literature has demonstrated that media conditions can cause a substantial difference in the efficacy of antibiotics and antimicrobials. Recent studies have also shown that minimum inhibitory concentration (MIC) tests performed in standard cell culture media...

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