Papers by William Gerwick
Phytochemistry, 2010
Two new epimers of malyngamide C, 8-O-acetyl-8-epi-malyngamide C (1) and 8-epi-malyngamide C (3) ... more Two new epimers of malyngamide C, 8-O-acetyl-8-epi-malyngamide C (1) and 8-epi-malyngamide C (3) have been isolated along with known compounds 6-O-acetylmalyngamide F (5), H (6), J (7) K (8), and characterized from a Grenada field collection of the marine cyanobacterium Lyngbya majuscula. The planar structures of these compounds were deduced by 1D-and 2D-NMR and mass spectral data interpretation. The absolute configurations were determined by a combination of CDspectroscopy, chemical degradation and the variable temperature Mosher's method. Compounds 1-5, 7 and 8 displayed moderate cytotoxicity to NCI-H460 human lung tumor and neuro-2a cancer cell lines, with IC 50 values ranging between 0.5 and 20 μg/mL.
Phytochemistry, 2010
Two new epimers of malyngamide C, 8-O-acetyl-8-epi-malyngamide C (1) and 8-epi-malyngamide C (3) ... more Two new epimers of malyngamide C, 8-O-acetyl-8-epi-malyngamide C (1) and 8-epi-malyngamide C (3) have been isolated along with known compounds 6-O-acetylmalyngamide F (5), H (6), J (7) K (8), and characterized from a Grenada field collection of the marine cyanobacterium Lyngbya majuscula. The planar structures of these compounds were deduced by 1D-and 2D-NMR and mass spectral data interpretation. The absolute configurations were determined by a combination of CDspectroscopy, chemical degradation and the variable temperature Mosher's method. Compounds 1-5, 7 and 8 displayed moderate cytotoxicity to NCI-H460 human lung tumor and neuro-2a cancer cell lines, with IC 50 values ranging between 0.5 and 20 μg/mL.
Lipids, Jan 1, 1992
Incubation of [1-14C]linolcic acid with an enzyme preparation obtained from the red alga Lithotha... more Incubation of [1-14C]linolcic acid with an enzyme preparation obtained from the red alga Lithothamnion corallioides CROUAN resulted in the formation of 11hydroxy-9(Z),12(Z)-octadecadienoic acid as well as smaller amounts of 9-hydroxy-10(E),12(Z)-octadecadienoic acid, 13-hydroxy-9(Z),11(E)-octadecadienoic acid and 11-ketw 9(Z),12(Z)~ctadecadienoic acid. Steric analysis showed that the 11-hydroxyoctadecadienoic acid had the (R) configuration. The 9-and l~hydroxyoctadecadienoic acids were not optically pure, but were due to mixtures of 75% (R) and 25% (S) enantiomers (9-hydroxyoctadecadienoate), and 24% (It) and 76% (S) enantiomers {13-hydroxyoctadecadienoate). U-Hydroxyoctadecadienoic acid was unstable at acidic pH. In acidified water, equal parts of 9(R,S)-hydroxy-lO(E),12(Z)-octadeeadienoate and 13(R,S)-hydroxy-9(Z),ll(E)q)ctadecadienoate, plus smaller amounts of the corresponding (E),(E) isomers were pro-
Nature Methods, 2009
Nonribosomal peptides (NRPs) are of great pharmacological importance, but there is currently no t... more Nonribosomal peptides (NRPs) are of great pharmacological importance, but there is currently no technology for high-throughput NRP dereplication and sequencing. We employ multi-stage mass spectrometry followed by spectral alignment algorithms for sequencing of cyclic NRPs. We also present an algorithm for comparative NRP dereplication that establishes similarities between newly isolated and previously identified similar but non-identical NRPs, substantially reducing dereplication efforts..
Analytical Chemistry, 2009
Natural and non-natural cyclic peptides are a crucial component in drug discovery programs becaus... more Natural and non-natural cyclic peptides are a crucial component in drug discovery programs because of their considerable pharmaceutical properties. Cyclosporin, microcystins, and nodularins are all notable pharmacologically important cyclic peptides. Because these biologically active peptides are often biosynthesized nonribosomally, they often contain nonstandard amino acids, thus increasing the complexity of the resulting tandem mass spectrometry data. In addition, because of the cyclic nature, the fragmentation patterns of many of these peptides showed much higher complexity when compared to related counterparts. Therefore, at the present time it is still difficult to annotate cyclic peptides MS/MS spectra. In this current work, an annotation program was developed for the annotation and characterization of tandem mass spectra obtained from cyclic peptides. This program, which we call MS-CPA is available as a web tool (http://lol.ucsd.edu/ms-cpa_v1/Input.py). Using this program, we have successfully annotated the sequence of representative cyclic peptides, such as seglitide, tyrothricin, desmethoxymajusculamide C, dudawalamide A, and cyclomarins, in a rapid manner and also were able to provide the first-pass structure evidence of a newly discovered natural product based on predicted sequence. This compound is not available in sufficient quantities for structural elucidation by other means such as NMR. 1 In addition to the development of this cyclic annotation program, it was observed that some cyclic peptides fragmented in unexpected ways resulting in the scrambling of sequences. In summary, MS-CPA not only provides a platform for rapid confirmation and annotation of tandem mass spectrometry data obtained with cyclic peptides but also enables quantitative analysis of the ion intensities. This program facilitates cyclic peptide analysis, sequencing, and also acts as a useful tool to investigate the uncommon fragmentation phenomena of cyclic peptides and aids the characterization of newly discovered cyclic peptides encountered in drug discovery programs.
PLoS ONE, 2011
Filamentous marine cyanobacteria are extraordinarily rich sources of structurally novel, biomedic... more Filamentous marine cyanobacteria are extraordinarily rich sources of structurally novel, biomedically relevant natural products. To understand their biosynthetic origins as well as produce increased supplies and analog molecules, access to the clustered biosynthetic genes that encode for the assembly enzymes is necessary. Complicating these efforts is the universal presence of heterotrophic bacteria in the cell wall and sheath material of cyanobacteria obtained from the environment and those grown in uni-cyanobacterial culture. Moreover, the high similarity in genetic elements across disparate secondary metabolite biosynthetic pathways renders imprecise current gene cluster targeting strategies and contributes sequence complexity resulting in partial genome coverage. Thus, it was necessary to use a dual-method approach of single-cell genomic sequencing based on multiple displacement amplification (MDA) and metagenomic library screening. Here, we report the identification of the putative apratoxin. A biosynthetic gene cluster, a potent cancer cell cytotoxin with promise for medicinal applications. The roughly 58 kb biosynthetic gene cluster is composed of 12 open reading frames and has a type I modular mixed polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS) organization and features loading and off-loading domain architecture never previously described. Moreover, this work represents the first successful isolation of a complete biosynthetic gene cluster from Lyngbya bouillonii, a tropical marine cyanobacterium renowned for its production of diverse bioactive secondary metabolites.
The Journal of Antibiotics, 2014
Most (75%) of the anti-infectives that save countless lives and enormously improve quality of lif... more Most (75%) of the anti-infectives that save countless lives and enormously improve quality of life originate from microbes found in nature. Herein, we described a global visualization of the detectable molecules produced from a single microorganism, which we define as the 'molecular network' of that organism, followed by studies to characterize the cellular effects of antibacterial molecules. We demonstrate that Streptomyces roseosporus produces at least four non-ribosomal peptide synthetase-derived molecular families and their gene subnetworks (daptomycin, arylomycin, napsamycin and stenothricin) were identified with different modes of action. A number of previously unreported analogs involving truncation, glycosylation, hydrolysis and biosynthetic intermediates and/or shunt products were also captured and visualized by creation of a map through MS/MS networking. The diversity of antibacterial compounds produced by S. roseosporus highlights the importance of developing new approaches to characterize the molecular capacity of an organism in a more global manner. This allows one to more deeply interrogate the biosynthetic capacities of microorganisms with the goal to streamline the discovery pipeline for biotechnological applications in agriculture and medicine. This is a contribution to a special issue to honor Chris Walsh's amazing career.
Proceedings of the National Academy of Sciences of the United States of America, Jan 24, 2011
Filamentous cyanobacteria of the genus Lyngbya are important contributors to coral reef ecosystem... more Filamentous cyanobacteria of the genus Lyngbya are important contributors to coral reef ecosystems, occasionally forming dominant cover and impacting the health of many other co-occurring organisms. Moreover, they are extraordinarily rich sources of bioactive secondary metabolites, with 35% of all reported cyanobacterial natural products deriving from this single pantropical genus. However, the true natural product potential and life strategies of Lyngbya strains are poorly understood because of phylogenetic ambiguity, lack of genomic information, and their close associations with heterotrophic bacteria and other cyanobacteria. To gauge the natural product potential of Lyngbya and gain insights into potential microbial interactions, we sequenced the genome of Lyngbya majuscula 3L, a Caribbean strain that produces the tubulin polymerization inhibitor curacin A and the molluscicide barbamide, using a combination of Sanger and 454 sequencing approaches. Whereas ∼ 293,000 nucleotides of...
Journal of Natural Products, 2015
Two new cyclic depsipeptides, companeramides A (1) and B (2), have been isolated from the phyloge... more Two new cyclic depsipeptides, companeramides A (1) and B (2), have been isolated from the phylogenetically characterized cyanobacterial collection that yielded the previously reported cancer cell toxin coibamide A (collected from Coiba Island, Panama). The planar structures of the companeramides, which contain 3-amino-2-methyl-7octynoic acid (Amoya), hydroxy isovaleric acid (Hiva), and eight α-amino acid units, were established by NMR spectroscopy and mass spectrometry. The absolute configuration of each companeramide was assigned using a combination of Marfey's methodology and chiral-phase HPLC analysis of complete and partial hydrolysis products compared to commercial and synthesized standards. Companeramides A (1) and B (2) showed high nanomolar in vitro antiplasmodial activity but were not overtly cytotoxic to four human cancer cell lines at the doses tested.
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Papers by William Gerwick