Protease Inhibitors from Microcystis aeruginosa Bloom Material Collected from the Dalton Reservoir, Israel
Abstract
Nine new metabolites, aeruginosins DA495A (1), DA511 (2), DA642A (3), DA642B (4), DA688 (5), DA722 (6), and DA495B (7), microguanidine DA368 (8), and anabaenopeptin DA850 (9), were isolated along with the known micropeptins MZ924, MZ939A, and MZ1019, cyanopeptolins S and SS, microcin SF608, and aeruginazoles DA1497, DA1304, and DA1274 from bloom material of the cyanobacterium Microcystis aeruginosa collected from the Dalton reservoir, Israel, in October 2007. Their structures were elucidated by a combination of various spectroscopic techniques, primarily NMR and MS, while the absolute configurations of the asymmetric centers were determined by Marfey's and chiral-phase HPLC methods. Two of the new aeruginosins, DA511 (1) and DA495A (2), contain a new Choi isomer, (2S,3aS,6S,7aS)-Choi. The structure elucidation and biological activities of the new metabolites are described.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cyanobacteria are a rich source of highly bioactive natural products, and in particular, protease inhibitors from numerous chemical classes.
“Cyanobacteria are known to be a rich source of highly bioactive natural products32–35, and in particular, protease inhibitors from numerous chemical classes36–41.”
From Native metabolomics identifies the rivulariapeptolide family of protease inhibitors (2022) · cites this paper as [41]
Cites
Determination ofD-amino acids. II. Use of a bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene
Marfey, P. S. (1984) · Carlsberg Research Communications · doi:10.1007/bf02908688 · Cited by 1,388 · see citing works
Marine cyanobacteria—a prolific source of natural products
Burja, A. M., Banaigs, B., Abou-Mansour, E., Grant Burgess, J., & Wright, P. C. (2001) · Tetrahedron · doi:10.1016/s0040-4020(01)00931-0 · Cited by 841 · see citing works
Ecotoxicological effects of selected cyanobacterial secondary metabolites a short review
Wiegand, C., & Pflugmacher, S. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.11.002 · Cited by 661 · see citing works
Pflugmacher, S., Wiegand, C., Oberemm, A., Beattie, K. A., Krause, E., Codd, G. A., & Steinberg, C. E. W. (1998) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(98)00107-x · Cited by 558 · see citing works
Bioactive natural products from marine cyanobacteria for drug discovery
Tan, L. T. (2007) · Phytochemistry · doi:10.1016/j.phytochem.2007.01.012 · Cited by 534 · see citing works
Proline Cis−Trans Isomerization and Protein Folding
Wedemeyer, W. J., Welker, E., & Scheraga, H. A. (2002) · Biochemistry · doi:10.1021/bi020574b · Cited by 446 · see citing works
Secondary Metabolites from Cyanobacteria: Complex Structures and Powerful Bioactivities
Gademann, K., & Portmann, C. (2008) · Current Organic Chemistry · doi:10.2174/138527208783743750 · Cited by 267 · see citing works
Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors
Ersmark, K., Valle, J. R. D., & Hanessian, S. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200605219 · Cited by 230 · see citing works
Pietsch, C., Wiegand, C., Amé, M. V., Nicklisch, A., Wunderlin, D. A., & Pflugmacher, S. (2001) · Environmental Toxicology · doi:10.1002/tox.10014 · Cited by 197 · see citing works
Harada, K., Fujii, K., Shimada, T., Suzuki, M., Sano, H., Adachi, K., & Carmichael, W. W. (1995) · Tetrahedron Letters · doi:10.1016/0040-4039(95)00073-l · Cited by 181 · see citing works
Oberemm, A., Fastner, J., & Steinberg, C. E. W. (1997) · Water Research · doi:10.1016/s0043-1354(97)00120-6 · Cited by 155 · see citing works
Murakami, M., Ishida, K., Okino, T., Okita, Y., Matsuda, H., & Yamaguchi, K. (1995) · Tetrahedron Letters · doi:10.1016/0040-4039(95)00396-t · Cited by 150 · see citing works
Murakami, M., Okita, Y., Matsuda, H., Okino, T., & Yamaguchi, K. (1994) · Tetrahedron Letters · doi:10.1016/s0040-4039(00)76848-1 · Cited by 140 · see citing works
Ishida, K., Christiansen, G., Yoshida, W. Y., Kurmayer, R., Welker, M., Valls, N., Bonjoch, J., Hertweck, C., Börner, T., Hemscheidt, T. K., et al. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.04.006 · Cited by 125 · see citing works
Non-Toxic Peptides from Toxic Cyanobacteria, Oscillatoria agardhii
Fujii, K., Sivonen, K., Naganawa, E., & Harada, K. (2000) · Tetrahedron · doi:10.1016/s0040-4020(99)01017-0 · Cited by 100 · see citing works
Wiegand, C., Peuthert, A., Pflugmacher, S., & Carmeli, S. (2002) · Environmental Toxicology · doi:10.1002/tox.10065 · Cited by 98 · see citing works
Self-citationMicropeptins A and B, plasmin and trypsin inhibitors from the blue-green alga Microcystis aeruginosa
Okino, T., Murakami, M., Haraguchi, R., Munekata, H., Matsuda, H., & Yamaguchi, K. (1993) · Tetrahedron Letters · doi:10.1016/s0040-4039(00)61471-5 · Cited by 97 · see citing works
Inhibitors of serine proteases from a waterbloom of the cyanobacterium Microcystis sp.
Banker, R., & Carmeli, S. (1999) · Tetrahedron · doi:10.1016/s0040-4020(99)00597-9 · Cited by 92 · see citing works
Self-citationMicroginins, Zinc Metalloproteases Inhibitors from the Cyanobacterium Microcystis aeruginosa
Ishida, K., Kato, T., Murakami, M., Watanabe, M., & Watanabe, M. F. (2000) · Tetrahedron · doi:10.1016/s0040-4020(00)00770-5 · Cited by 89 · see citing works
Gkelis, S., Harjunpää, V., Lanaras, T., & Sivonen, K. (2005) · Environmental Toxicology · doi:10.1002/tox.20105 · Cited by 77 · see citing works
Mádi, Z. L., Griesinger, C., & Ernst, R. R. (1990) · Journal of the American Chemical Society · doi:10.1021/ja00164a010 · Cited by 70 · see citing works
Metabolites of Microcystis aeruginosa Bloom Material from Lake Kinneret, Israel
Lifshits, M., & Carmeli, S. (2012) · Journal of Natural Products · doi:10.1021/np200909x · Cited by 56 · see citing works
Self-citationShin, H. J., Matsuda, H., Murakami, M., & Yamaguchi, K. (1997) · Journal of Natural Products · doi:10.1021/np960597p · Cited by 52 · see citing works
Valls, N., Vallribera, M., Carmeli, S., & Bonjoch, J. (2003) · Organic Letters · doi:10.1021/ol0273250 · Cited by 48 · see citing works
Self-citationJakobi, C., RINEHART, K. L. J., Neuber, R., Mez, K., & Weckesser, J. (1996) · Phycologia · doi:10.2216/i0031-8884-35-6s-111.1 · Cited by 46 · see citing works
Three novel metabolites from a bloom of the cyanobacterium Microcystis sp.
Gesner-Apter, S., & Carmeli, S. (2008) · Tetrahedron · doi:10.1016/j.tet.2008.05.031 · Cited by 45 · see citing works
Self-citationNew microviridins from a water bloom of the cyanobacterium Microcystis aeruginosa
Reshef, V., & Carmeli, S. (2006) · Tetrahedron · doi:10.1016/j.tet.2006.05.028 · Cited by 44 · see citing works
Self-citationCyanopeptolin S, a sulfate-containing depsipeptide from a water bloom ofMicrocystissp.
Jakobi, C., Oberer, L., Quiquerez, C., König, W. A., & Weckesser, J. (1995) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1995.tb07569.x · Cited by 43 · see citing works
Micropeptins from an Israeli Fishpond Water Bloom of the Cyanobacterium Microcystis sp.
Zafrir, E., & Carmeli, S. (2009) · Journal of Natural Products · doi:10.1021/np900546u · Cited by 35 · see citing works
Self-citationNew aeruginazoles, a group of thiazole-containing cyclic peptides from Microcystis aeruginosa blooms
Adiv, S., Ahronov-Nadborny, R., & Carmeli, S. (2011) · Tetrahedron · doi:10.1016/j.tet.2011.12.045 · Cited by 26 · see citing works
Self-citationVegman, M., & Carmeli, S. (2013) · Tetrahedron · doi:10.1016/j.tet.2013.09.054 · Cited by 19 · see citing works
Self-citationTwo novel biological active modified peptides from the cyanobacterium Microcystis sp.
Raveh, A., & Carmeli, S. (2008) · Phytochemistry Letters · doi:10.1016/j.phytol.2008.10.002 · Cited by 17 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Natural Products from Cyanobacteria: Focus on Beneficial Activities
Demay, J., Bernard, C., Reinhardt, A., & Marie, B. (2019) · Marine Drugs · doi:10.3390/md17060320 · Cited by 331 · see citing works
Cyanobacterial bioactive metabolites—A review of their chemistry and biology
Huang, I., & Zimba, P. V. (2019) · Harmful Algae · doi:10.1016/j.hal.2018.11.008 · Cited by 183 · see citing works
Cyanobacterial bioactive metabolites—A review of their chemistry and biology
Huang, I., & Zimba, P. V. (2019) · Harmful Algae · doi:10.1016/j.hal.2019.05.001 · Cited by 93 · see citing works
Qian, H., Zhang, M., Liu, G., Lu, T., Sun, L., & Pan, X. (2018) · Chemosphere · doi:10.1016/j.chemosphere.2018.09.156 · Cited by 60 · see citing works
Schreuder, H., Liesum, A., Loenze, P., Stump, H., Hoffmann, H., Schiell, M., Kurz, M. E., Toti, L., Bauer, A., Kallus, C., et al. (2016) · Scientific Reports · doi:10.1038/srep32958 · Cited by 59 · see citing works
Thuấn, N. H., An, T. T., Shrestha, A., Canh, N. X., Sohng, J. K., & Dhakal, D. (2019) · Frontiers in Chemistry · doi:10.3389/fchem.2019.00604 · Cited by 56 · see citing works
Simultaneous Production of Anabaenopeptins and Namalides by the Cyanobacterium Nostoc sp. CENA543
Shishido, T. K., Jokela, J., Fewer, D. P., Wahlsten, M., Fiore, M. F., & Sivonen, K. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00570 · Cited by 52 · see citing works
Elkobi-Peer, S., & Carmeli, S. (2015) · Marine Drugs · doi:10.3390/md13042347 · Cited by 49 · see citing works
Self-citationNative metabolomics identifies the rivulariapeptolide family of protease inhibitors
Reher, R., Aron, A. T., Fajtová, P., Stincone, P., Wagner, B., Pérez-Lorente, A. I., Liu, C., Shalom, I. Y. B., Bittremieux, W., Wang, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32016-6 · Cited by 53 · see citing works
Sanz, M., Andreote, A. P. D., Fiore, M. F., Dörr, F. A., & Pinto, E. (2015) · Marine Drugs · doi:10.3390/md13063892 · Cited by 45 · see citing works
Pancrace, C., Ishida, K., Briand, E., Picchi, D. G., Weiz, A. R., Guljamow, A., Scalvenzi, T., Sassoon, N., Hertweck, C., Dittmann, E., et al. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.8b00918 · Cited by 34 · see citing works
de Lima, S. T., Alvarenga, D. O., Etchegaray, A., Fewer, D. P., Jokela, J., Varani, A. M., Sanz, M., Dörr, F. A., Pinto, E., Sivonen, K., et al. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.6b00948 · Cited by 32 · see citing works
Anabaenopeptins from Cyanobacteria in Freshwater Bodies of Greece
Zervou, S., Kaloudis, T., Gkelis, S., Hiskia, A. E., & Mazur‐Marzec, H. (2021) · Toxins · doi:10.3390/toxins14010004 · Cited by 29 · see citing works
Chemical diversity of cyanobacterial natural products
Weiss, M. B., Borges, R. M., Sullivan, P., Domingues, J. P. B., da Silva, F. H., Trindade, V. G. S., Luo, S., Orjala, J., & Crnkovic, C. M. (2024) · Natural Product Reports · doi:10.1039/d4np00040d · Cited by 31 · see citing works
Vegman, M., & Carmeli, S. (2014) · Tetrahedron · doi:10.1016/j.tet.2014.07.057 · Cited by 28 · see citing works
Self-citationLiu, J., Zhang, M., Huang, Z., Fang, J., Wang, Z., Zhou, C., & Qiu, X. (2023) · Marine Drugs · doi:10.3390/md21040217 · Cited by 25 · see citing works
Duan, Y., Xiong, D., Li, Y., Dong, H., Wang, W., & Zhang, J. (2020) · Aquaculture · doi:10.1016/j.aquaculture.2020.735444 · Cited by 22 · see citing works
Total Synthesis and Structural Revision of Aeruginosin KT608A
Scherer, M., & Gademann, K. (2017) · Organic Letters · doi:10.1021/acs.orglett.7b01822 · Cited by 20 · see citing works
Huang, I., Pietrasiak, N., Gobler, C. J., Johansen, J. R., Burkholder, J. M., D’Antonio, S., & Zimba, P. V. (2021) · Harmful Algae · doi:10.1016/j.hal.2021.102116 · Cited by 19 · see citing works
He, Y., Chen, Y., Tao, H., Zhou, X., Liu, J., Liu, Y., & Yang, B. (2024) · Phytochemistry Reviews · doi:10.1007/s11101-024-09960-w · Cited by 19 · see citing works
Burberg, C., Petzoldt, T., & von Elert, E. (2020) · Toxins · doi:10.3390/toxins12010033 · Cited by 15 · see citing works
Hasan-Amer, R., & Carmeli, S. (2017) · Marine Drugs · doi:10.3390/md15120371 · Cited by 15 · see citing works
Self-citationAnabaenopeptins from Nostoc edaphicum CCNP1411
Konkel, R., Grabski, M., Cegłowska, M., Wieczerzak, E., Węgrzyn, G., & Mazur‐Marzec, H. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph191912346 · Cited by 13 · see citing works
Detection of secondary cyanobacterial metabolites using LC-HRMS in Lake Karaoun
Zervou, S., Hammoud, N. A., Godin, S., Hiskia, A. E., Szpunar, J., & Łobiński, R. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.164725 · Cited by 13 · see citing works
Daphnia populations are similar but not identical in tolerance to different protease inhibitors
Schwarzenberger, A., Ilíć, M., & von Elert, E. (2021) · Harmful Algae · doi:10.1016/j.hal.2021.102062 · Cited by 13 · see citing works
Problems and Prospects of Applications of Cyanobacteria (Review)
Polyak, Y. M., & Сухаревич, В. И. (2023) · Inland Water Biology · doi:10.1134/s1995082923010121 · Cited by 13 · see citing works
A novel route towards cycle-tail peptides using oxime resin: teaching an old dog a new trick
Bérubé, C., Borgia, A., & Voyer, N. (2018) · Organic & Biomolecular Chemistry · doi:10.1039/c8ob01868e · Cited by 12 · see citing works
Yang, H., Gu, X., Chen, H., Zeng, Q., Mao, Z., Ge, Y., & Yao, Y.-J. (2024) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2024.109961 · Cited by 10 · see citing works
Determination of FVIIa-sTF Inhibitors in Toxic Microcystis Cyanobacteria by LC-MS Technique
Anas, A. R. J., Nakajima, A., Naruse, C., Tone, M., Asukabe, H., & Harada, K. (2015) · Marine Drugs · doi:10.3390/md14010007 · Cited by 10 · see citing works
Other Cyanobacterial Bioactive Substances
Eleršek, T., Bláha, L., Mazur‐Marzec, H., Schmidt, W., & Carmeli, S. (2016) · Wiley eBooks · doi:10.1002/9781119068761.ch19 · Cited by 8 · see citing works
Self-citationOverlingė, D., Cegłowska, M., Konkel, R., & Mazur‐Marzec, H. (2024) · Marine Drugs · doi:10.3390/md22110506 · Cited by 7 · see citing works
Specialized metabolites from cyanobacteria and their biological activities
Kumla, D., Sousa, M. E., Vasconcelos, V. M., & Kijjoa, A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821491-6.00002-8 · Cited by 5 · see citing works
Algor, S. W., Sukenik, A., & Carmeli, S. (2024) · Marine Drugs · doi:10.3390/md22090389 · Cited by 3 · see citing works
Self-citationBérubé, C., Guay, L.-D., Fraser, T., Lapointe, V., Cardinal, S., & Biron, É. (2023) · Organic & Biomolecular Chemistry · doi:10.1039/d3ob01608k · Cited by 3 · see citing works
Effects of climate change on metabolite accumulation in freshwater and marine cyanobacteria
Huang, I., Hu, X., Abdulla, H. A. N., & Zimba, P. V. (2021) · Climate Change Ecology · doi:10.1016/j.ecochg.2021.100018 · Cited by 2 · see citing works
Hasin, O., & Carmeli, S. (2018) · Natural Product Communications · doi:10.1177/1934578x1801301020
Self-citationProblems and Prospects of Applications of Cyanobacteria (Review)
Polyak, Y. M., & Сухаревич, В. И. (2023) · Inland Water Biology · doi:10.31857/s032096522301014x
Distinct ecotoxicological impairs induced by different Microcystis genotypes to Medaka fishPreprint
Marie, B., Meur, M. L., Duval, C., Quiquand, M., Emilie Lance, A., & Duperron, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.24.630230
Premathilaka, S. H., & Isailović, D. (2025) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.5c00165
Li, X., Zhang, B., & Qiu, X. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110228
- Authors
- Adiv, S., & Carmeli, S.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Carmeli, Shmuel
- ORCID
- Carmeli, Shmuel
- Venue
- Journal of Natural Products
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-11-21
- Volume
- 76
- Issue
- 12
- Pages
- 2307-2315
- ISSN
- 0163-3864 (ISSN-L)
- 1520-6025
- OpenAlex
- W2326291014
- Cited by
- 41
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 1
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Natural Products (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Physical Sciences › Environmental Science › Environmental Chemistry › Aquatic Ecosystems and Phytoplankton Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
- Keywords
- Microcystis aeruginosa, cyanobacterial blooms, protease inhibitors, aeruginosins, cyanopeptolins, anabaenopeptins, structure elucidation, absolute configuration
- MeSH terms
- Chromatography, High Pressure Liquid, Israel, Oligopeptides, Peptides, Peptides, Cyclic, Protease Inhibitors, Trypsin Inhibitors, Molecular Structure, Nuclear Magnetic Resonance, Biomolecular, Microcystis, Depsipeptides
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
