Marcel Jaspars

Find an error

Name:

Organization: University of Aberdeen , England

Department: Department of Chemistry

Title: (PhD)

TOPICS

Organic Chemistry

Chemicals
References

Accurate quantification of modified cyclic peptides without the need for authentic standards

Co-reporter:Rosemary I. Adaba, Greg Mann, Andrea Raab, Wael E. Houssen, Andrew R. McEwan, Louise Thomas, Jioji Tabudravu, James H. Naismith, Marcel Jaspars

Tetrahedron 2016 Volume 72(Issue 52) pp:8603-8609

Publication Date(Web):29 December 2016

DOI:10.1016/j.tet.2016.11.040

There is a growing interest in the use of cyclic peptides as therapeutics, but their efficient production is often the bottleneck in taking them forward in the development pipeline. We have recently developed a method to synthesise azole-containing cyclic peptides using enzymes derived from different cyanobactin biosynthetic pathways. Accurate quantification is crucial for calculation of the reaction yield and for the downstream biological testing of the products. In this study, we demonstrate the development and validation of two methods to accurately quantify these compounds in the reaction mixture and after purification. The first method involves the use of a HPLC coupled in parallel to an ESMS and an ICP-MS, hence correlating the calculated sulfur content to the amount of cyclic peptide. The second method is an NMR ERETIC method for quantifying the solution concentration of cyclic peptides. These methods make the quantification of new compounds much easier as there is no need for the use of authentic standards when they are not available.

Legonaridin, a new member of linaridin RiPP from a Ghanaian Streptomyces isolate

Co-reporter:Mostafa E. Rateb, Yin Zhai, Emmanuelle Ehrner, Christopher M. Rath, Xiaoling Wang, Jioji Tabudravu, Rainer Ebel, Mervin Bibb, Kwaku Kyeremeh, Pieter C. Dorrestein, Kui Hong, Marcel Jaspars and Hai Deng

Organic & Biomolecular Chemistry 2015 vol. 13(Issue 37) pp:9585-9592

Publication Date(Web):31 Jul 2015

DOI:10.1039/C5OB01269D

Linaridins are rare linear ribosomally-synthesized and post-translationally modified peptides (RiPPs) and only two, cypemycin and SGR-1832, in this family have been identified so far. Legonaridin 1 has been discovered as a new member of linaridins through chemical isolation, peptidogenomics, comprehensive 1- and 2-D NMR and advanced Marfey's analyses from the soil bacterium Streptomyces sp. CT34, an isolate collected from Legon, Ghana. Bioinformatics analysis of the gene cluster suggested that the biosynthesis of legonaridin 1 is different from those of cypemycin and SGR-1832. Consistent with bioinformatics and peptidogenomics analyses, 1 has a total of nine post-modifications, 8 dehydrobutyrine residues and a N,N-dimethylated N-terminus with a carboxylic acid at the C-terminus. Legonaridin 1 is structurally different from the two known linaridins comprising a new subfamily. This is the first time that NMR spectroscopy is used to establish the 2-D structure of a linaridin RiPP.

Scalarane sesterterpenes from the Egyptian Red Sea sponge Phyllospongia lamellosa

Co-reporter:Marwa H.A. Hassan, Mostafa E. Rateb, Mona Hetta, Tarek A. Abdelaziz, Mohamed A. Sleim, Marcel Jaspars, Rabab Mohammed

Tetrahedron 2015 Volume 71(Issue 4) pp:577-583

Publication Date(Web):28 January 2015

DOI:10.1016/j.tet.2014.12.035

Biology and HRESIMS-guided screening of the dichloromethane fraction of the marine sponge Phyllospongia lamellosa collected from the Red Sea resulted in the isolation and characterization of five new scalarane sesterterpenes; phyllospongins A–E (1–5), in addition to four known derivatives, 12α-acetoxy-20,24-dimethyl-25-norscalar-16-en-24-one (6), 12α-acetoxy-13β,18β-cyclobutan-20,24-dimethyl-24-oxoscalar-16-en-25β-ol (7), 12α-acetoxy-24,25-epoxy-24-hydroxy-20,24-dimethylscalarane (8), and scalardysin-A (9) that were previously isolated from Carteriospongia sp. and Dysidea sp. The structures of the isolated compounds were fully characterized using NMR spectroscopic techniques and mass spectrometric analysis. All the isolated compounds were tested for their cytotoxic activity against human cancer cell lines (HePG-2, MCF-7, and HCT-116) and antibacterial activity against some Gram-positive and Gram-negative strains.

Dermacozines H–J Isolated from a Deep-Sea Strain of Dermacoccus abyssi from Mariana Trench Sediments

Co-reporter:Marcell Wagner ; Wael M. Abdel-Mageed ; Rainer Ebel ; Alan T. Bull ; Michael Goodfellow ; Hans-Peter Fiedler

Journal of Natural Products 2014 Volume 77(Issue 2) pp:416-420

Publication Date(Web):February 5, 2014

DOI:10.1021/np400952d

Dermacoccus abyssi sp. nov. strains MT1.1 and MT1.2 are actinomycetes isolated from a Mariana Trench sediment at a depth of 10 898 m. The fermentation process using complex media led to the production of three new pigmented heteroaromatic (oxidized and reduced) phenazine compounds, dermacozines H–J (1–3). Extensive use was made of 1D and 2D NMR experiments and high-resolution MS to determine the structures of the compounds. The new dermacozines showed radical scavenging activity, and the highest activity was observed for dermacozine H (1), with an IC50 value of 18.8 μM.

An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides

Co-reporter:Dr. Wael E. Houssen;Andrew F. Bent;Dr. Andrew R. McEwan;Nathalie Pieiller;Dr. Jioji Tabudravu;Dr. Jesko Koehnke;Greg Mann;Rosemary I. Adaba;Dr. Louise Thomas;Dr. Usama W. Hawas;Dr. Huanting Liu;Dr. Ulrich Schwarz-Linek; Margaret C. M. Smith; James H. Naismith; Marcel Jaspars

Angewandte Chemie International Edition 2014 Volume 53( Issue 51) pp:14171-14174

Publication Date(Web):

DOI:10.1002/anie.201408082

Abstract

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.

An Enzymatic Route to Selenazolines

Co-reporter:Dr. Jesko Koehnke;Falk Morawitz;Andrew F. Bent;Dr. Wael E. Houssen;Dr. Sally L. Shirran;Dr. Matthew A. Fuszard;Dr. Iain A. Smellie;Dr. Catherine H. Botting; Margaret C. M. Smith; Marcel Jaspars; James H. Naismith

ChemBioChem 2013 Volume 14( Issue 5) pp:564-567

Publication Date(Web):

DOI:10.1002/cbic.201300037

A Combined Atomic Force Microscopy and Computational Approach for the Structural Elucidation of Breitfussin A and B: Highly Modified Halogenated Dipeptides from Thuiaria breitfussi

Co-reporter:Kine Ø. Hanssen;Bruno Schuler;Dr. Antony J. Williams;Taye B. Demissie;Dr. Espen Hansen;Dr. Jeanette H. Andersen;Dr. Johan Svenson;Kirill Blinov;Dr. Michal Repisky;Dr. Fabian Mohn;Dr. Gerhard Meyer;Dr. John-Sigurd Svendsen;Dr. Kenneth Ruud;Dr. Mikhail Elyashberg;Dr. Leo Gross;Dr. Marcel Jaspars;Dr. Johan Isaksson

Angewandte Chemie 2012 Volume 124( Issue 49) pp:12404-12407

Publication Date(Web):

DOI:10.1002/ange.201203960

The Discovery of New Cyanobactins from Cyanothece PCC 7425 Defines a New Signature for Processing of Patellamides

Co-reporter:Dr. Wael E. Houssen;Dr. Jesko Koehnke;David Zollman;Dr. Jeremie Vendome;Dr. Andrea Raab; Margaret C. M. Smith; James H. Naismith; Marcel Jaspars

ChemBioChem 2012 Volume 13( Issue 18) pp:2683-2689

Publication Date(Web):

DOI:10.1002/cbic.201200661

Abstract

Cyanobactins, including patellamides, are a group of cyanobacterial post-translationally modified ribosomal cyclic peptides. The final product should in theory be predictable from the sequence of the precursor peptide and the associated tailoring enzymes. Understanding the mechanism and recognition requirements of these enzymes will allow their rational engineering. We have identified three new cyanobactins from a Cyanothece PCC 7425 culture subjected to a heat shock. One of these compounds revealed a novel signature signal for ThcA, the subtilisin-like serine protease that is homologous to the patellamide protease PatA. The crystal structure of the latter and modelling studies allow rationalisation of the recognition determinants for both enzymes, consistent with the ribosomal biosynthetic origin of the new compounds.

Cover Picture: The Discovery of New Cyanobactins from Cyanothece PCC 7425 Defines a New Signature for Processing of Patellamides (ChemBioChem 18/2012)

Co-reporter:Dr. Wael E. Houssen;Dr. Jesko Koehnke;David Zollman;Dr. Jeremie Vendome;Dr. Andrea Raab; Margaret C. M. Smith; James H. Naismith; Marcel Jaspars

ChemBioChem 2012 Volume 13( Issue 18) pp:

Publication Date(Web):

DOI:10.1002/cbic.201290074

A Combined Atomic Force Microscopy and Computational Approach for the Structural Elucidation of Breitfussin A and B: Highly Modified Halogenated Dipeptides from Thuiaria breitfussi

Angewandte Chemie International Edition 2012 Volume 51( Issue 49) pp:12238-12241

Publication Date(Web):

DOI:10.1002/anie.201203960

New nodulopeptins from Nodularia spumigena KAC 66

Co-reporter:Marc Schumacher, Neil Wilson, Jioji N. Tabudravu, Christine Edwards, Linda A. Lawton, Cherie Motti, Anthony D. Wright, Marc Diederich, Marcel Jaspars

Tetrahedron 2012 68(5) pp: 1622-1628

Publication Date(Web):

DOI:10.1016/j.tet.2011.11.056

Chaxamycins A–D, Bioactive Ansamycins from a Hyper-arid Desert Streptomyces sp.

Co-reporter:Mostafa E. Rateb, Wael E. Houssen, Markus Arnold, Mostafa H. Abdelrahman, Hai Deng, William T. A. Harrison, Chinyere K. Okoro, Juan A. Asenjo, Barbara A. Andrews, Gail Ferguson, Alan T. Bull, Michael Goodfellow, Rainer Ebel, and Marcel Jaspars

Journal of Natural Products 2011 Volume 74(Issue 6) pp:1491-1499

Publication Date(Web):May 9, 2011

DOI:10.1021/np200320u

Streptomyces sp. strain C34, isolated from soil collected in the Chilean hyper-arid Atacama Desert, was cultured on different media, resulting in the isolation and identification of four new ansamycin-type polyketides. The organism was selected for chemical investigation on the basis of a genome-mining PCR-based experiment targeting the gene encoding rifamycin-specific 3-amino-5-hydroxybenzoic acid synthetase (AHBA). The isolated compounds were structurally characterized using NMR and MS techniques and named chaxamycins A–D (1–4). Compounds 1–4 were tested for their antibacterial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 and for their ability to inhibit the intrinsic ATPase activity of the heat shock protein 90 (Hsp90). Chaxamycin D (4), which showed a selective antibacterial activity against S. aureus ATCC 25923, was tested further against a panel of MRSA clinical isolates. In a virtual screening experiment, chaxamycins A–D (1–4) have also been docked into the ATP-binding pocket in the N-terminal domain of the Hsp90, and the observed interactions are discussed.

Diverse Metabolic Profiles of a Streptomyces Strain Isolated from a Hyper-arid Environment

Co-reporter:Mostafa E. Rateb, Wael E. Houssen, William T. A. Harrison, Hai Deng, Chinyere K. Okoro, Juan A. Asenjo, Barbara A. Andrews, Alan T. Bull, Michael Goodfellow, Rainer Ebel, and Marcel Jaspars

Journal of Natural Products 2011 Volume 74(Issue 9) pp:1965-1971

Publication Date(Web):August 31, 2011

DOI:10.1021/np200470u

The metabolic profile of Streptomyces sp. strain C34, isolated from the Chilean hyper-arid Atacama Desert soil, is dependent on the culture media used for its growth. The application of an OSMAC approach on this strain using a range of cultivation media resulted in the isolation and identification of three new compounds from the rare class of 22-membered macrolactone polyketides, named chaxalactins A–C (1–3). In addition, the known compounds deferroxamine E (4), hygromycin A (5), and 5″-dihydrohygromycin A (6) were detected. The isolated compounds were characterized by NMR spectroscopy and accurate mass spectrometric analysis. Compounds 1–3 displayed strong activity against Gram-positive but weak activity Gram-negative strains tested.

Dermacozines, a new phenazine family from deep-sea dermacocci isolated from a Mariana Trench sediment

Co-reporter:Wael M. Abdel-Mageed, Bruce F. Milne, Marcell Wagner, Marc Schumacher, Peter Sandor, Wasu Pathom-aree, Michael Goodfellow, Alan T. Bull, Koki Horikoshi, Rainer Ebel, Marc Diederich, Hans-Peter Fiedler and Marcel Jaspars

Organic & Biomolecular Chemistry 2010 vol. 8(Issue 10) pp:2352-2362

Publication Date(Web):18 Mar 2010

DOI:10.1039/C001445A

Dermacoccus abyssi sp. nov., strains MT1.1 and MT1.2 are actinomycetes isolated from Mariana Trench sediment at a depth of 10898 m. Fermentation using ISP2 and 410 media, respectively, lead to production of seven new oxidized and reduced phenazine-type pigments, dermacozines A–G (1–7), together with the known phenazine-1-carboxylic acid (8) and phenazine-1,6-dicarboxylic acid (9). Extensive use was made of 1D and 2D-NMR data, and high resolution MS to determine the structures of the compounds. To confirm the structure of the most complex pentacyclic analogue (5) we made use of electronic structure calculations to compare experimental and theoretical UV-Vis spectra, which confirmed a novel structural class of phenazine derivatives, the dermacozines. The absolute stereochemistry of dermacozine D (4) was determined as S by a combination of CD spectroscopy and electronic structure calculations. Dermacozines F (6) and G (7) exhibited moderate cytotoxic activity against leukaemia cell line K562 with IC50 values of 9 and 7 μM, respectively, while the highest radical scavenger activity was observed for dermacozine C (3) with an IC50 value of 8.4 μM.

Inside Cover: Azole-Based Cyclic Peptides from the Sea Squirt Lissoclinum Patella: Old Scaffolds, New Avenues (ChemBioChem 13/2010)

Co-reporter:Wael E. Houssen Dr. Dr.

ChemBioChem 2010 Volume 11( Issue 13) pp:

Publication Date(Web):

DOI:10.1002/cbic.201090062

Solution Structure of the Leader Sequence of the Patellamide Precursor Peptide, PatE134

Co-reporter:Wael E. Houssen Dr.;Stephen H. Wright Dr.;Arnout P. Kalverda Dr.;Gary S. Thompson Dr.;Sharon M. Kelly Dr.

ChemBioChem 2010 Volume 11( Issue 13) pp:1867-1873

Publication Date(Web):

DOI:10.1002/cbic.201000305

Abstract

The solution structure of the leader sequence of the patellamide precursor peptide was analysed by using CD and determined with NOE-restrained molecular dynamics calculations. This leader sequence is highly conserved in the precursor peptides of some other cyanobactins harbouring heterocycles, and is assumed to play a role in targeting the precursor peptide to the post-translational machinery. The sequence was observed to form an α-helix spanning residues 13–28 with a hydrophobic surface on one side of the helix. This hydrophobic surface is proposed to be the site of the initial binding with modifying enzymes.

Azole-Based Cyclic Peptides from the Sea Squirt Lissoclinum Patella: Old Scaffolds, New Avenues

Co-reporter:Wael E. Houssen Dr. Dr.

ChemBioChem 2010 Volume 11( Issue 13) pp:1803-1815

Publication Date(Web):

DOI:10.1002/cbic.201000230

Laurefurenynes A–F, new Cyclic Ether Acetogenins from a Marine Red Alga, Laurencia sp.

Co-reporter:Wael M. Abdel-Mageed, Rainer Ebel, Fred A. Valeriote, Marcel Jaspars

Tetrahedron 2010 66(15) pp: 2855-2862

Publication Date(Web):

DOI:10.1016/j.tet.2010.02.041

Chemical synthesis and biological activities of 3-alkyl pyridinium polymeric analogues of marine toxins

Co-reporter:Wael E. Houssen;Zhibao Lu;RuAngelie Edrada-Ebel

Journal of Chemical Biology 2010 Volume 3( Issue 3) pp:113-125

Publication Date(Web):2010 August

DOI:10.1007/s12154-010-0036-4

Two new large poly-1,3-dodecylpyridinium salts, APS12 and APS12-2 of 12.5- and 14.7-kDa size, respectively, were synthesised and tested for their pore-forming and transfection capabilities in HEK 293 and undifferentiated mouse ES cells using patch-clamp recording, Ca2+ imaging and flow cytometry. Polymerisation reactions were enhanced by microwaves, and the product sizes were controlled by altering the irradiation time. This method can also be applied to obtain polymers with variable linking chains as shown by the preparation of poly-(1,3-octylpyridinium) salt of 11.9-kDa size. Molecular weights of the final products were determined using ESIMS analysis, which also indicated the products to be amongst the largest macro-cycles ever recorded, up to a 900-membered ring. Anti-bacterial, haemolytic and anti-acetylcholinesterase activities were also reported for the two dodecyl pyridinium polymers. These biological activities are characteristic to the structurally related marine toxin, poly-APS.

Bioactive Diterpene Derivatives from the Marine Sponge Spongionella sp.

Co-reporter:Mostafa E. Rateb, Wael E. Houssen, Marc Schumacher, William T. A. Harrison, Marc Diederich, Rainer Ebel and Marcel Jaspars

Journal of Natural Products 2009 Volume 72(Issue 8) pp:1471-1476

Publication Date(Web):July 14, 2009

DOI:10.1021/np900233c

Three new compounds of the rare classes trisnorditerpenes, bisnorditerpenes, and norditerpenes, gracilins J−L (1, 2, 6), and a new diterpene, 3′-norspongiolactone (8), were isolated from the extract of the marine sponge Spongionella sp. using NMR- and bioassay-guided fractionation, in addition to three known gracilins (3−5) as well as the known diterpenoid tetrahydroaplysulphurin-1 (7). The structures were elucidated using NMR spectroscopic techniques and mass spectrometric analysis. The structure of gracilin H (3) was confirmed by single-crystal X-ray analysis. All compounds were tested for their cytotoxicity and for their potential to inhibit EGF-R tyrosine kinase.

New iodotyramine derivatives from Didemnum rubeum

Co-reporter:Godofredo Solano, Cherie A. Motti, Marcel Jaspars

Tetrahedron 2009 65(36) pp: 7482-7486

Publication Date(Web):

DOI:10.1016/j.tet.2009.07.002

NF-κB-Inhibiting Naphthopyrones from the Fijian Echinoderm Comanthus parvicirrus

Co-reporter:Florence Folmer, William T. A. Harrison, Jioji N. Tabudravu, Marcel Jaspars, William Aalbersberg, Klaus Feussner, Anthony D. Wright, Mario Dicato and Marc Diederich

Journal of Natural Products 2008 Volume 71(Issue 1) pp:106-111

Publication Date(Web):December 19, 2007

DOI:10.1021/np070290y

The two naphthopyrones 6-methoxycomaparvin (1) and 6-methoxycomaparvin 5-methyl ether (2) were isolated from a bioactive methanol-soluble extract of the Fijian echinoderm Comanthus parvicirrus. Their structures were assigned on the basis of spectroscopic methods. X-ray diffraction analysis was used to confirm the structure of 1. Both compounds were tested for their potential to inhibit the activation of the transcription factor NF-κB, which plays an important role in cancer development and inflammation, and the mechanism of action of the two compounds was investigated. Both naphthopyrones 1 and 2 completely inhibit TNF-α-induced NF-κB activation at a concentration of 300 µM by inhibiting the enzymatic activity of the kinase IKKβ.

Marine Metabolites and Metal Ion Chelation: Intact Recovery and Identification of an Iron(II) Complex in the Extract of the Ascidian Eudistoma gilboviride

Co-reporter:StephenH. Wright Dr.;Andrea Raab Dr.;JiojiN. Tabudravu Dr.;Jörg Feldmann ;PaulF. Long Dr.;ChristopherN. Battershill Dr.;WalterC. Dunlap Dr.;BruceF. Milne Dr.

Angewandte Chemie International Edition 2008 Volume 47( Issue 42) pp:8090-8092

Publication Date(Web):

DOI:10.1002/anie.200802060

Novel Bioactive Metabolites from a Marine Derived Bacterium Nocardia sp. ALAA 2000

Co-reporter:Mervat M A El-Gendy, Usama W Hawas and Marcel Jaspars

The Journal of Antibiotics 2008 61(6) pp:379-386

Publication Date(Web):2008-06-01

DOI:10.1038/ja.2008.53

Extracts of the Egyptian marine actinomycete, Nocardia sp. ALAA 2000, were found to be highly bioactive. It was isolated from the marine red alga Laurenica spectabilis collected off the Ras-Gharib coast of the Red Sea, Egypt. According to detailed identification studies, the strain was classified as a member of the genus Nocardia. The cultivation and chemical analysis of this species yielded four structurally related compounds namely, chrysophanol 8-methyl ether (1), asphodelin; 4,7′-bichrysophanol (2) and justicidin B (3), in addition to a novel bioactive compound ayamycin; 1,1-dichloro-4-ethyl-5-(4-nitro-phenyl)-hexan-2-one (4) which is unique in contain both chlorination and a rarely observed nitro group. The compounds were isolated by a series of chromatographic steps and their structures of 1~3 secured by detailed spectroscopic analysis of the MS and NMR data whereas that of 4 was elucidated by single crystal X-ray diffraction studies. These compounds displayed different potent antimicrobial activity against both Gram-positive and Gram-negative bacteria as well as fungi with MIC ranging from 0.1 to 10 μg/ml.

Spontaneity in the patellamide biosynthetic pathway

Co-reporter:Bruce F. Milne, Paul F. Long, Antonio Starcevic, Daslav Hranueli and Marcel Jaspars

Organic & Biomolecular Chemistry 2006 vol. 4(Issue 4) pp:631-638

Publication Date(Web):09 Jan 2006

DOI:10.1039/B515938E

Post-translationally modified ribosomal peptides are unusual natural products and many have potent biological activity. The biosynthetic processes involved in their formation have been delineated for some, but the patellamides represent a unique group of these metabolites with a combination of a macrocycle, small heterocycles and D-stereocentres. The genes encoding for the patellamides show very low homology to known biosynthetic genes and there appear to be no explicit genes for the macrocyclisation and epimerisation steps. Using a combination of literature data and large-scale molecular dynamics calculations with explicit solvent, we propose that the macrocyclisation and epimerisation steps are spontaneous and interdependent and a feature of the structure of the linear peptide. Our study suggests the steps in the biosynthetic route are heterocyclisation, macrocyclisation, followed by epimerisation and finally dehydrogenation. This study is presented as testable hypothesis based on literature and theoretical data to be verified by future detailed experimental investigations.

Conformational studies of free and Li+ complexed jasplakinolide, a cyclic depsipeptide from the Fijian marine sponge Jaspis splendens

Co-reporter:Jioji N. Tabudravu, Linda A. Morris, Bruce F. Milne and Marcel Jaspars

Organic & Biomolecular Chemistry 2005 vol. 3(Issue 5) pp:745-749

Publication Date(Web):07 Feb 2005

DOI:10.1039/B416839A

The complexation of Li+ to jasplakinolide, a marine sponge derived cyclic depsipeptide showed preferential binding to two out of four carbonyl oxygens (C-10, C-14) and the electrons of the aromatic system of the β-tyrosine amino acid residue. This is in contrast to previous results obtained by others who proposed complexation to three out of four available carbonyl oxygens (C-1, C-10, C-14). The structure of the complex in CD3CN was determined by NOE restrained molecular dynamic calculations. Structures of the uncomplexed jasplakinolide were calculated in CDCl3 and CD3CN for comparison.

Shotgun Cloning and Heterologous Expression of the Patellamide Gene Cluster as a Strategy to Achieving Sustained Metabolite Production

Co-reporter:Paul F. Long Dr.;Walter C. Dunlap Dr.;Christopher N. Battershill Dr.

ChemBioChem 2005 Volume 6(Issue 10) pp:

Publication Date(Web):29 JUN 2005

DOI:10.1002/cbic.200500210

Shotgun cloning into E. coli of genomic DNA from Prochloron sp., symbiont of the seasquirt Lissoclinum patella, resulted in the heterologous expression of the patellamide gene cluster and subsequent production of patellamide D (1) and ascidiacyclamide (2) at levels of 80–100 ng mL⁻¹.

Conformational change in the thiazole and oxazoline containing cyclic octapeptides, the patellamides. Part 2. Solvent dependent conformational change

Co-reporter:Bruce F. Milne, Linda A. Morris, Marcel Jaspars and Gary S. Thompson

Organic & Biomolecular Chemistry 2002 (Issue 6) pp:1076-1080

Publication Date(Web):24 Apr 2002

DOI:10.1039/B201824C

Solvent dependent conformational change of the thiazole and oxazoline containing cyclic peptides, the patellamides, is examined by a combination of experimental and theoretical methods. A mechanism for the simultaneous formation of two type-II β-turns in the patellamides is proposed based on molecular dynamics and NOE restrained molecular dynamics studies as well as literature evidence. The effect of the solvent and desymmetrisation of the patellamides is crucial, with symmetrical patellamides in polar solvents giving the open type-I conformation, whereas symmetrical patellamides in non-polar solvents and asymmetrical patellamides in both polar and non-polar solvents give rise to the folded type-II conformation.

Conformational change in the thiazole and oxazoline containing cyclic octapeptides, the patellamides. Part 1. Cu2+ and Zn2+ induced conformational change

Co-reporter:Linda A. Morris, Bruce F. Milne, Gary S. Thompson and Marcel Jaspars

Organic & Biomolecular Chemistry 2002 (Issue 6) pp:1072-1075

Publication Date(Web):24 Apr 2002

DOI:10.1039/B201823N

Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline containing cyclic octapeptides, the patellamides, is examined by a combination of experimental and theoretical methods. Circular dichroism and NOE-restrained molecular dynamics studies indicate that upon complexing with one equivalent of Cu2+, patellamide C undergoes a change in conformation which pre-organises a second Cu2+ binding site, and that the binding of a second Cu2+ induces no further conformational change. The binding of Zn2+ induces little conformational change in patellamide C. A restrained conformational search shows that the conformational change induced by the addition of one equivalent of Cu2+ to patellamide C is an intrinsic design feature of the system. Electronic structure calculations indicate that the patellamides provide an ideal coordination environment for Cu2+. On the basis of the evidence gathered, it can be proposed that Cu2+ is the biologically relevant metal for the patellamides.

Legonaridin, a new member of linaridin RiPP from a Ghanaian Streptomyces isolate

Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 37) pp:NaN9592-9592

Publication Date(Web):2015/07/31

DOI:10.1039/C5OB01269D

Dermacozines, a new phenazine family from deep-sea dermacocci isolated from a Mariana Trench sediment

Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 10) pp:NaN2362-2362

Publication Date(Web):2010/03/18

DOI:10.1039/C001445A