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Kaarina Sivonen
Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Helsinki, Finland

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Paper
Published: 04 June 2021 in Organic & Biomolecular Chemistry
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Laxaphycins are a family of cyclic lipopeptides with synergistic antifungal and antiproliferative activities.

ACS Style

Lassi Matti Petteri Heinilä; David Peter Fewer; Jouni Kalevi Jokela; Matti Wahlsten; Xiaodan Ouyang; Perttu Permi; Anna Jortikka; Kaarina Sivonen. The structure and biosynthesis of heinamides A1–A3 and B1–B5, antifungal members of the laxaphycin lipopeptide family. Organic & Biomolecular Chemistry 2021, 1 .

AMA Style

Lassi Matti Petteri Heinilä, David Peter Fewer, Jouni Kalevi Jokela, Matti Wahlsten, Xiaodan Ouyang, Perttu Permi, Anna Jortikka, Kaarina Sivonen. The structure and biosynthesis of heinamides A1–A3 and B1–B5, antifungal members of the laxaphycin lipopeptide family. Organic & Biomolecular Chemistry. 2021; ():1.

Chicago/Turabian Style

Lassi Matti Petteri Heinilä; David Peter Fewer; Jouni Kalevi Jokela; Matti Wahlsten; Xiaodan Ouyang; Perttu Permi; Anna Jortikka; Kaarina Sivonen. 2021. "The structure and biosynthesis of heinamides A1–A3 and B1–B5, antifungal members of the laxaphycin lipopeptide family." Organic & Biomolecular Chemistry , no. : 1.

Journal article
Published: 24 May 2021 in Marine Drugs
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Sponges form symbiotic relationships with diverse and abundant microbial communities. Cyanobacteria are among the most important members of the microbial communities that are associated with sponges. Here, we performed a genus-wide comparative genomic analysis of the newly described marine benthic cyanobacterial genus Leptothoe (Synechococcales). We obtained draft genomes from Le. kymatousa TAU-MAC 1615 and Le. spongobia TAU-MAC 1115, isolated from marine sponges. We identified five additional Leptothoe genomes, host-associated or free-living, using a phylogenomic approach, and the comparison of all genomes showed that the sponge-associated strains display features of a symbiotic lifestyle. Le. kymatousa and Le. spongobia have undergone genome reduction; they harbored considerably fewer genes encoding for (i) cofactors, vitamins, prosthetic groups, pigments, proteins, and amino acid biosynthesis; (ii) DNA repair; (iii) antioxidant enzymes; and (iv) biosynthesis of capsular and extracellular polysaccharides. They have also lost several genes related to chemotaxis and motility. Eukaryotic-like proteins, such as ankyrin repeats, playing important roles in sponge-symbiont interactions, were identified in sponge-associated Leptothoe genomes. The sponge-associated Leptothoe stains harbored biosynthetic gene clusters encoding novel natural products despite genome reduction. Comparisons of the biosynthetic capacities of Leptothoe with chemically rich cyanobacteria revealed that Leptothoe is another promising marine cyanobacterium for the biosynthesis of novel natural products.

ACS Style

Despoina Konstantinou; Rafael Popin; David Fewer; Kaarina Sivonen; Spyros Gkelis. Genome Reduction and Secondary Metabolism of the Marine Sponge-Associated Cyanobacterium Leptothoe. Marine Drugs 2021, 19, 298 .

AMA Style

Despoina Konstantinou, Rafael Popin, David Fewer, Kaarina Sivonen, Spyros Gkelis. Genome Reduction and Secondary Metabolism of the Marine Sponge-Associated Cyanobacterium Leptothoe. Marine Drugs. 2021; 19 (6):298.

Chicago/Turabian Style

Despoina Konstantinou; Rafael Popin; David Fewer; Kaarina Sivonen; Spyros Gkelis. 2021. "Genome Reduction and Secondary Metabolism of the Marine Sponge-Associated Cyanobacterium Leptothoe." Marine Drugs 19, no. 6: 298.

Preprint content
Published: 11 December 2020
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Background Microbial natural products have unique chemical structures and diverse biological activities. Cyanobacteria commonly possess a wide range of biosynthetic gene clusters to produce natural products. Several studies have mapped the distribution of natural product biosynthetic gene clusters in cyanobacterial genomes. However, little attention has been paid to natural product biosynthesis in plasmids. Some genes encoding cyanobacterial natural product biosynthetic pathways are believed to be dispersed by plasmids through horizontal gene transfer. Thus, we examined complete cyanobacterial genomes to assess if plasmids are involved in the production and dissemination of natural products by cyanobacteria.Results The 185 analyzed genomes possessed 1 to 42 gene clusters and an average of 10. In total, 1816 biosynthetic gene clusters were found. Approximately 95% of these clusters were present in chromosomes. The remaining 5% were present in plasmids, from which homologs of the biosynthetic pathways for aeruginosin, anabaenopeptin, ambiguine, cryptophycin, hassallidin, geosmin, and microcystin were manually curated. The cryptophycin pathway was previously described as active while the other gene cluster include all genes for biosynthesis. Approximately 12% of the 424 analyzed cyanobacterial plasmids contained homologs of genes involved in conjugation. Large plasmids, previously named as “chromids”, were also observed to be widespread in cyanobacteria. Sixteen cryptic natural product biosynthetic gene clusters and geosmin biosynthetic gene clusters were located in those mobile plasmids.Conclusion Homologues of genes involved in the production of toxins, protease inhibitors, odorous compounds, antimicrobials, antitumorals, and other unidentified natural products are located in cyanobacterial plasmids. Some of these plasmids are predicted to be conjugative. The present study provides in silico evidence that plasmids are involved in the distribution of natural product biosynthetic pathways in cyanobacteria.

ACS Style

Rafael Popin; Danillo Alvarenga; Raquel Castelo-Branco; David Fewer; Kaarina Sivonen. Mining of Cyanobacterial Genomes Indicates That Plasmids Are Involved in the Production of Natural Products. 2020, 1 .

AMA Style

Rafael Popin, Danillo Alvarenga, Raquel Castelo-Branco, David Fewer, Kaarina Sivonen. Mining of Cyanobacterial Genomes Indicates That Plasmids Are Involved in the Production of Natural Products. . 2020; ():1.

Chicago/Turabian Style

Rafael Popin; Danillo Alvarenga; Raquel Castelo-Branco; David Fewer; Kaarina Sivonen. 2020. "Mining of Cyanobacterial Genomes Indicates That Plasmids Are Involved in the Production of Natural Products." , no. : 1.

Original research article
Published: 16 September 2020 in Frontiers in Microbiology
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Cyanobacteria produce a wide range of lipopeptides that exhibit potent membrane-disrupting activities. Laxaphycins consist of two families of structurally distinct macrocyclic lipopeptides that act in a synergistic manner to produce antifungal and antiproliferative activities. Laxaphycins are produced by range of cyanobacteria but their biosynthetic origins remain unclear. Here, we identified the biosynthetic pathways responsible for the biosynthesis of the laxaphycins produced by Scytonema hofmannii PCC 7110. We show that these laxaphycins, called scytocyclamides, are produced by this cyanobacterium and are encoded in a single biosynthetic gene cluster with shared polyketide synthase enzymes initiating two distinct non-ribosomal peptide synthetase pathways. The unusual mechanism of shared enzymes synthesizing two distinct types of products may aid future research in identifying and expressing natural product biosynthetic pathways and in expanding the known biosynthetic logic of this important family of natural products.

ACS Style

Lassi Matti Petteri Heinilä; David P. Fewer; Jouni Kalevi Jokela; Matti Wahlsten; Anna Jortikka; Kaarina Sivonen. Shared PKS Module in Biosynthesis of Synergistic Laxaphycins. Frontiers in Microbiology 2020, 11, 1 .

AMA Style

Lassi Matti Petteri Heinilä, David P. Fewer, Jouni Kalevi Jokela, Matti Wahlsten, Anna Jortikka, Kaarina Sivonen. Shared PKS Module in Biosynthesis of Synergistic Laxaphycins. Frontiers in Microbiology. 2020; 11 ():1.

Chicago/Turabian Style

Lassi Matti Petteri Heinilä; David P. Fewer; Jouni Kalevi Jokela; Matti Wahlsten; Anna Jortikka; Kaarina Sivonen. 2020. "Shared PKS Module in Biosynthesis of Synergistic Laxaphycins." Frontiers in Microbiology 11, no. : 1.

Website
Published: 26 August 2020 in Artificial Recharge of Groundwater
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ACS Style

K. Lahti; J. Vaitomaa; A-L. Kivimaki; Kaarina Sivonen. Fate of cyanobacterial hepatotoxins in artificial recharge of groundwater and in bank filtration. Artificial Recharge of Groundwater 2020, 211 -216.

AMA Style

K. Lahti, J. Vaitomaa, A-L. Kivimaki, Kaarina Sivonen. Fate of cyanobacterial hepatotoxins in artificial recharge of groundwater and in bank filtration. Artificial Recharge of Groundwater. 2020; ():211-216.

Chicago/Turabian Style

K. Lahti; J. Vaitomaa; A-L. Kivimaki; Kaarina Sivonen. 2020. "Fate of cyanobacterial hepatotoxins in artificial recharge of groundwater and in bank filtration." Artificial Recharge of Groundwater , no. : 211-216.

Preprint content
Published: 30 May 2020
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Cyanobacteria produce a wide range of lipopeptides that exhibit potent membrane-disrupting activities. Laxaphycins consist of two families of structurally distinct macrocyclic lipopeptides that act in a synergistic manner to produce antifungal and antiproliferative activities. Laxaphycins are produced by range of cyanobacteria but their biosynthetic origins remain unclear. Here, we identified the biosynthetic pathways responsible for the biosynthesis of the laxaphycins produced by Scytonema hofmannii PCC 7110. We show that these laxaphycins, called scytocyclamides, are produced by this cyanobacterium and are encoded in a single biosynthetic gene cluster with shared polyketide synthase enzymes initiating two distinct non-ribosomal peptide synthetase pathways. To our knowledge, laxaphycins are the first clearly distinct polyketide synthase and non-ribosomal peptide synthetase hybrid natural products with shared branched biosynthesis. The unusual mechanism of shared enzymes synthesizing two distinct types of products may aid future research in identifying and expressing natural product biosynthetic pathways and in expanding the known biosynthetic logic of this important family of natural products.

ACS Style

Lassi Matti Petteri Heinilä; David P Fewer; Jouni Kalevi Jokela; Matti Wahlsten; Anna Jortikka; Kaarina Sivonen. Shared PKS modules in biosynthesis of synergistic laxaphycins. 2020, 1 .

AMA Style

Lassi Matti Petteri Heinilä, David P Fewer, Jouni Kalevi Jokela, Matti Wahlsten, Anna Jortikka, Kaarina Sivonen. Shared PKS modules in biosynthesis of synergistic laxaphycins. . 2020; ():1.

Chicago/Turabian Style

Lassi Matti Petteri Heinilä; David P Fewer; Jouni Kalevi Jokela; Matti Wahlsten; Anna Jortikka; Kaarina Sivonen. 2020. "Shared PKS modules in biosynthesis of synergistic laxaphycins." , no. : 1.

Journal article
Published: 27 May 2020 in PeerJ
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Background Brasilonema is a cyanobacterial genus found on the surface of mineral substrates and plants such as bromeliads, orchids and eucalyptus. B. octagenarum stands out among cyanobacteria due to causing damage to the leaves of its host in an interaction not yet observed in other cyanobacteria. Previous studies revealed that B. octagenaum UFV-E1 is capable of leading eucalyptus leaves to suffer internal tissue damage and necrosis by unknown mechanisms. This work aimed to investigate the effects of B. octagenarum UFV-E1 inoculation on Eucalyptus urograndis and to uncover molecular mechanisms potentially involved in leaf damage by these cyanobacteria using a comparative genomics approach. Results Leaves from E. urograndis saplings were exposed for 30 days to B. octagenarum UFV-E1, which was followed by the characterization of its genome and its comparison with the genomes of four other Brasilonema strains isolated from phyllosphere and the surface of mineral substrates. While UFV-E1 inoculation caused an increase in root and stem dry mass of the host plants, the sites colonized by cyanobacteria on leaves presented a significant decrease in pigmentation, showing that the cyanobacterial mats have an effect on leaf cell structure. Genomic analyses revealed that all evaluated Brasilonema genomes harbored genes encoding molecules possibly involved in plant-pathogen interactions, such as hydrolases targeting plant cell walls and proteins similar to known virulence factors from plant pathogens. However, sequences related to the type III secretory system and effectors were not detected, suggesting that, even if any virulence factors could be expressed in contact with their hosts, they would not have the structural means to actively reach plant cytoplasm. Conclusions Leaf damage by this species is likely related to the blockage of access to sunlight by the efficient growth of cyanobacterial mats on the phyllosphere, which may hinder the photosynthetic machinery and prevent access to some essential molecules. These results reveal that the presence of cyanobacteria on leaf surfaces is not as universally beneficial as previously thought, since they may not merely provide the products of nitrogen fixation to their hosts in exchange for physical support, but in some cases also hinder regular leaf physiology leading to tissue damage.

ACS Style

Danillo Alvarenga; Maione W. Franco; Kaarina Sivonen; Marli F. Fiore; Alessandro M. Varani. Evaluating Eucalyptus leaf colonization by Brasilonema octagenarum (Cyanobacteria, Scytonemataceae) using in planta experiments and genomics. PeerJ 2020, 8, e9158 .

AMA Style

Danillo Alvarenga, Maione W. Franco, Kaarina Sivonen, Marli F. Fiore, Alessandro M. Varani. Evaluating Eucalyptus leaf colonization by Brasilonema octagenarum (Cyanobacteria, Scytonemataceae) using in planta experiments and genomics. PeerJ. 2020; 8 ():e9158.

Chicago/Turabian Style

Danillo Alvarenga; Maione W. Franco; Kaarina Sivonen; Marli F. Fiore; Alessandro M. Varani. 2020. "Evaluating Eucalyptus leaf colonization by Brasilonema octagenarum (Cyanobacteria, Scytonemataceae) using in planta experiments and genomics." PeerJ 8, no. : e9158.

Preprint content
Published: 16 April 2020
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Cyanobacteria form harmful mass blooms in freshwater and marine environments around the world. A range of secondary metabolites has been identified from cultures of cyanobacteria and biomass collected from cyanobacterial bloom events. A comprehensive database is necessary to correctly identify cyanobacterial metabolites and advance research on their abundance, persistence and toxicity in natural environments. We consolidated open access databases and manually curated missing information from the literature published between 1970 and March 2020. The result is the database CyanoMetDB, which includes more than 2000 entries based on more than 750 literature references. This effort has more than doubled the total number of entries with complete literature metadata and structural composition (SMILES codes) compared to publicly available databases to this date. Over the past decade, more than one hundred additional secondary metabolites have been identified yearly. We organized all entries into structural classes and conducted substructure searches of the provided SMILES codes. This approach demonstrated, for example, that 65% of the compounds carry at least one peptide bond, 57% are cyclic compounds, and 30% carry at least one halogen atom. Structural searches by SMILES code can be further specified to identify structural motifs that are relevant for analytical approaches, research on biosynthetic pathways, bioactivity-guided analysis, or to facilitate predictive science and modeling efforts on cyanobacterial metabolites. This database facilitates rapid identification of cyanobacterial metabolites from toxic blooms, research on the biosynthesis of cyanobacterial natural products, and the identification of novel natural products from cyanobacteria.

ACS Style

Martin R. Jones; Ernani Pinto; Mariana A. Torres; Fabiane Doerr; Hanna Mazur-Marzec; Karolina Szubert; Luciana Tartaglione; Carmela Dell’Aversano; Christopher O. Miles; Daniel G. Beach; Pearse McCarron; Kaarina Sivonen; David P. Fewer; Jouni Jokela; Elisabeth M.-L. Janssen. Comprehensive database of secondary metabolites from cyanobacteria. 2020, 1 .

AMA Style

Martin R. Jones, Ernani Pinto, Mariana A. Torres, Fabiane Doerr, Hanna Mazur-Marzec, Karolina Szubert, Luciana Tartaglione, Carmela Dell’Aversano, Christopher O. Miles, Daniel G. Beach, Pearse McCarron, Kaarina Sivonen, David P. Fewer, Jouni Jokela, Elisabeth M.-L. Janssen. Comprehensive database of secondary metabolites from cyanobacteria. . 2020; ():1.

Chicago/Turabian Style

Martin R. Jones; Ernani Pinto; Mariana A. Torres; Fabiane Doerr; Hanna Mazur-Marzec; Karolina Szubert; Luciana Tartaglione; Carmela Dell’Aversano; Christopher O. Miles; Daniel G. Beach; Pearse McCarron; Kaarina Sivonen; David P. Fewer; Jouni Jokela; Elisabeth M.-L. Janssen. 2020. "Comprehensive database of secondary metabolites from cyanobacteria." , no. : 1.

Journal article
Published: 11 April 2020 in Toxins
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Cyanobacteria produce an array of toxins that pose serious health risks to humans and animals. The closely related diazotrophic genera, Anabaena, Dolichospermum and Aphanizomenon, frequently form poisonous blooms in lakes and brackish waters around the world. These genera form a complex now termed the Anabaena, Dolichospermum and Aphanizomenon (ADA) clade and produce a greater array of toxins than any other cyanobacteria group. However, taxonomic confusion masks the distribution of toxin biosynthetic pathways in cyanobacteria. Here we obtained 11 new draft genomes to improve the understanding of toxin production in these genera. Comparison of secondary metabolite pathways in all available 31 genomes for these three genera suggests that the ability to produce microcystin, anatoxin-a, and saxitoxin is associated with specific subgroups. Each toxin gene cluster was concentrated or even limited to a certain subgroup within the ADA clade. Our results indicate that members of the ADA clade encode a variety of secondary metabolites following the phylogenetic clustering of constituent species. The newly sequenced members of the ADA clade show that phylogenetic separation of planktonic Dolichospermum and benthic Anabaena is not complete. This underscores the importance of taxonomic revision of Anabaena, Dolichospermum and Aphanizomenon genera to reflect current phylogenomic understanding.

ACS Style

Julia Österholm; Rafael V. Popin; David P. Fewer; Kaarina Sivonen. Phylogenomic Analysis of Secondary Metabolism in the Toxic Cyanobacterial Genera Anabaena, Dolichospermum and Aphanizomenon. Toxins 2020, 12, 248 .

AMA Style

Julia Österholm, Rafael V. Popin, David P. Fewer, Kaarina Sivonen. Phylogenomic Analysis of Secondary Metabolism in the Toxic Cyanobacterial Genera Anabaena, Dolichospermum and Aphanizomenon. Toxins. 2020; 12 (4):248.

Chicago/Turabian Style

Julia Österholm; Rafael V. Popin; David P. Fewer; Kaarina Sivonen. 2020. "Phylogenomic Analysis of Secondary Metabolism in the Toxic Cyanobacterial Genera Anabaena, Dolichospermum and Aphanizomenon." Toxins 12, no. 4: 248.

Journal article
Published: 26 March 2020 in Toxins
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Global warming, paired with eutrophication processes, is shifting phytoplankton communities towards the dominance of bloom-forming and potentially toxic cyanobacteria. The ecosystems of shallow lakes are especially vulnerable to these changes. Traditional monitoring via microscopy is not able to quantify the dynamics of toxin-producing cyanobacteria on a proper spatio-temporal scale. Molecular tools are highly sensitive and can be useful as an early warning tool for lake managers. We quantified the potential microcystin (MC) producers in Lake Peipsi using microscopy and quantitative polymerase chain reaction (qPCR) and analysed the relationship between the abundance of the mcyE genes, MC concentration, MC variants and toxin quota per mcyE gene. We also linked environmental factors to the cyanobacteria community composition. In Lake Peipsi, we found rather moderate MC concentrations, but microcystins and microcystin-producing cyanobacteria were widespread across the lake. Nitrate (NO3−) was a main driver behind the cyanobacterial community at the beginning of the growing season, while in late summer it was primarily associated with the soluble reactive phosphorus (SRP) concentration. A positive relationship was found between the MC quota per mcyE gene and water temperature. The most abundant variant—MC-RR—was associated with MC quota per mcyE gene, while other MC variants did not show any significant impact.

ACS Style

Kristel Panksep; Marju Tamm; Evanthia Mantzouki; Anne Rantala-Ylinen; Reet Laugaste; Kaarina Sivonen; Olga Tammeorg; Veljo Kisand. Using Microcystin Gene Copies to Determine Potentially-Toxic Blooms, Example from a Shallow Eutrophic Lake Peipsi. Toxins 2020, 12, 211 .

AMA Style

Kristel Panksep, Marju Tamm, Evanthia Mantzouki, Anne Rantala-Ylinen, Reet Laugaste, Kaarina Sivonen, Olga Tammeorg, Veljo Kisand. Using Microcystin Gene Copies to Determine Potentially-Toxic Blooms, Example from a Shallow Eutrophic Lake Peipsi. Toxins. 2020; 12 (4):211.

Chicago/Turabian Style

Kristel Panksep; Marju Tamm; Evanthia Mantzouki; Anne Rantala-Ylinen; Reet Laugaste; Kaarina Sivonen; Olga Tammeorg; Veljo Kisand. 2020. "Using Microcystin Gene Copies to Determine Potentially-Toxic Blooms, Example from a Shallow Eutrophic Lake Peipsi." Toxins 12, no. 4: 211.

Journal article
Published: 25 February 2020 in Toxins
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The bloom-forming cyanobacterium Nodularia spumigena CENA596 encodes the biosynthetic gene clusters (BGCs) of the known natural products nodularins, spumigins, anabaenopeptins/namalides, aeruginosins, mycosporin-like amino acids, and scytonemin, along with the terpenoid geosmin. Targeted metabolomics confirmed the production of these metabolic compounds, except for the alkaloid scytonemin. Genome mining of N. spumigena CENA596 and its three closely related Nodularia strains—two planktonic strains from the Baltic Sea and one benthic strain from Japanese marine sediment—revealed that the number of BGCs in planktonic strains was higher than in benthic one. Geosmin—a volatile compound with unpleasant taste and odor—was unique to the Brazilian strain CENA596. Automatic annotation of the genomes using subsystems technology revealed a related number of coding sequences and functional roles. Orthologs from the Nodularia genomes are involved in the primary and secondary metabolisms. Phylogenomic analysis of N. spumigena CENA596 based on 120 conserved protein sequences positioned this strain close to the Baltic Nodularia. Phylogeny of the 16S rRNA genes separated the Brazilian CENA596 strain from those of the Baltic Sea, despite their high sequence identities (99% identity, 100% coverage). The comparative analysis among planktic Nodularia strains showed that their genomes were considerably similar despite their geographically distant origin.

ACS Style

Rafael Vicentini Popin; Endrews Delbaje; Vinicius Augusto Carvalho De Abreu; Janaina Rigonato; Felipe Augusto Dörr; Ernani Pinto; Kaarina Sivonen; Marli Fatima Fiore. Genomic and Metabolomic Analyses of Natural Products in Nodularia spumigena Isolated from a Shrimp Culture Pond. Toxins 2020, 12, 141 .

AMA Style

Rafael Vicentini Popin, Endrews Delbaje, Vinicius Augusto Carvalho De Abreu, Janaina Rigonato, Felipe Augusto Dörr, Ernani Pinto, Kaarina Sivonen, Marli Fatima Fiore. Genomic and Metabolomic Analyses of Natural Products in Nodularia spumigena Isolated from a Shrimp Culture Pond. Toxins. 2020; 12 (3):141.

Chicago/Turabian Style

Rafael Vicentini Popin; Endrews Delbaje; Vinicius Augusto Carvalho De Abreu; Janaina Rigonato; Felipe Augusto Dörr; Ernani Pinto; Kaarina Sivonen; Marli Fatima Fiore. 2020. "Genomic and Metabolomic Analyses of Natural Products in Nodularia spumigena Isolated from a Shrimp Culture Pond." Toxins 12, no. 3: 141.

Journal article
Published: 24 December 2019 in Toxins
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Cyanobacteria are photosynthetic organisms that produce a large diversity of natural products with interesting bioactivities for biotechnological and pharmaceutical applications. Cyanobacterial extracts exhibit toxicity towards other microorganisms and cancer cells and, therefore, represent a source of potentially novel natural products for drug discovery. We tested 62 cyanobacterial strains isolated from various Brazilian biomes for antileukemic and antimicrobial activities. Extracts from 39 strains induced selective apoptosis in acute myeloid leukemia (AML) cancer cell lines. Five of these extracts also exhibited antifungal and antibacterial activities. Chemical and dereplication analyses revealed the production of nine known natural products. Natural products possibly responsible for the observed bioactivities and five unknown, chemically related chlorinated compounds present only in Brazilian cyanobacteria were illustrated in a molecular network. Our results provide new information on the vast biosynthetic potential of cyanobacteria isolated from Brazilian environments.

ACS Style

Tania Keiko Shishido; Rafael Vicentini Popin; Jouni Jokela; Matti Wahlsten; Marli Fatima Fiore; David P. Fewer; Lars Herfindal; Kaarina Sivonen. Dereplication of Natural Products with Antimicrobial and Anticancer Activity from Brazilian Cyanobacteria. Toxins 2019, 12, 12 .

AMA Style

Tania Keiko Shishido, Rafael Vicentini Popin, Jouni Jokela, Matti Wahlsten, Marli Fatima Fiore, David P. Fewer, Lars Herfindal, Kaarina Sivonen. Dereplication of Natural Products with Antimicrobial and Anticancer Activity from Brazilian Cyanobacteria. Toxins. 2019; 12 (1):12.

Chicago/Turabian Style

Tania Keiko Shishido; Rafael Vicentini Popin; Jouni Jokela; Matti Wahlsten; Marli Fatima Fiore; David P. Fewer; Lars Herfindal; Kaarina Sivonen. 2019. "Dereplication of Natural Products with Antimicrobial and Anticancer Activity from Brazilian Cyanobacteria." Toxins 12, no. 1: 12.

Journal article
Published: 06 December 2019 in Proceedings of the National Academy of Sciences
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Medicinal plants are a prolific source of natural products with remarkable chemical and biological properties, many of which have considerable remedial benefits. Numerous medicinal plants are suffering from wildcrafting, and thus biotechnological production processes of their natural products are urgently needed. The plantAster tataricusis widely used in traditional Chinese medicine and contains unique active ingredients named astins. These are macrocyclic peptides showing promising antitumor activities and usually containing the highly unusual moiety 3,4-dichloroproline. The biosynthetic origins of astins are unknown despite being studied for decades. Here we show that astins are produced by the recently discovered fungal endophyteCyanodermella asteris. We were able to produce astins in reasonable and reproducible amounts using axenic cultures of the endophyte. We identified the biosynthetic gene cluster responsible for astin biosynthesis in the genome ofC. asterisand propose a production pathway that is based on a nonribosomal peptide synthetase. Striking differences in the production profiles of endophyte and host plant imply a symbiotic cross-species biosynthesis pathway for astin C derivatives, in which plant enzymes or plant signals are required to trigger the synthesis of plant-exclusive variants such as astin A. Our findings lay the foundation for the sustainable biotechnological production of astins independent from aster plants.

ACS Style

Thomas Schafhauser; Linda Jahn; Norbert Kirchner; Andreas Kulik; Liane Flor; Alexander Lang; Thibault Caradec; David P. Fewer; Kaarina Sivonen; Willem J. H. van Berkel; Philippe Jacques; Tilmann Weber; Harald Gross; Karl-Heinz van Pée; Wolfgang Wohlleben; Jutta Ludwig-Müller. Antitumor astins originate from the fungal endophyteCyanodermella asterisliving within the medicinal plantAster tataricus. Proceedings of the National Academy of Sciences 2019, 116, 26909 -26917.

AMA Style

Thomas Schafhauser, Linda Jahn, Norbert Kirchner, Andreas Kulik, Liane Flor, Alexander Lang, Thibault Caradec, David P. Fewer, Kaarina Sivonen, Willem J. H. van Berkel, Philippe Jacques, Tilmann Weber, Harald Gross, Karl-Heinz van Pée, Wolfgang Wohlleben, Jutta Ludwig-Müller. Antitumor astins originate from the fungal endophyteCyanodermella asterisliving within the medicinal plantAster tataricus. Proceedings of the National Academy of Sciences. 2019; 116 (52):26909-26917.

Chicago/Turabian Style

Thomas Schafhauser; Linda Jahn; Norbert Kirchner; Andreas Kulik; Liane Flor; Alexander Lang; Thibault Caradec; David P. Fewer; Kaarina Sivonen; Willem J. H. van Berkel; Philippe Jacques; Tilmann Weber; Harald Gross; Karl-Heinz van Pée; Wolfgang Wohlleben; Jutta Ludwig-Müller. 2019. "Antitumor astins originate from the fungal endophyteCyanodermella asterisliving within the medicinal plantAster tataricus." Proceedings of the National Academy of Sciences 116, no. 52: 26909-26917.

Research article
Published: 01 November 2019 in ACS Chemical Biology
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Prenylation is a common step in the biosynthesis of many natural products and plays an important role in increasing their structural diversity and enhancing biological activity. Muscoride A is a linear peptide alkaloid that contain two contiguous oxazoles and unusual prenyl groups that protect the amino and carboxy termini. Here we identified the 12.7 kb muscoride (mus) biosynthetic gene clusters from Nostoc spp. PCC 7906 and UHCC 0398. The mus biosynthetic gene clus-ters encode enzymes for the heterocyclization, oxidation, and prenylation of the MusE precursor protein. The mus gene clusters encodes two copies of the cyanobactin prenyltransfer-ase, MusF1 and MusF2. The predicted tetrapeptide substrate of MusF1 and MusF2 was synthesized through a novel tandem cyclization route in only eight steps. Biochemical assays demonstrated that MusF1 acts on the carboxy-terminus while MusF2 acts on the amino-terminus of the tetrapeptide sub-strate. We show that the MusF2 enzyme catalyzes the reverse or forward prenylation of amino-termini from Nostoc sp. PCC 7906 and UHCC 0398, respectively. This finding expands the regiospecific chemical functionality of cyanobactin prenyl-transferases and the chemical diversity of the cyanobactin family of natural products to include bis-prenylated polyoxa-zole linear peptides.

ACS Style

Antti Mattila; Rose-Marie Andsten; Mikael Jumppanen; Michele Assante; Jouni Jokela; Matti Wahlsten; Kornelia M. Mikula; Cihad Sigindere; Daniel H. Kwak; Muriel Gugger; Harri Koskela; Kaarina Sivonen; Xinyu Liu; Jari Yli-Kauhaluoma; Hideo Iwaï; David P. Fewer. Biosynthesis of the Bis-Prenylated Alkaloids Muscoride A and B. ACS Chemical Biology 2019, 14, 2683 -2690.

AMA Style

Antti Mattila, Rose-Marie Andsten, Mikael Jumppanen, Michele Assante, Jouni Jokela, Matti Wahlsten, Kornelia M. Mikula, Cihad Sigindere, Daniel H. Kwak, Muriel Gugger, Harri Koskela, Kaarina Sivonen, Xinyu Liu, Jari Yli-Kauhaluoma, Hideo Iwaï, David P. Fewer. Biosynthesis of the Bis-Prenylated Alkaloids Muscoride A and B. ACS Chemical Biology. 2019; 14 (12):2683-2690.

Chicago/Turabian Style

Antti Mattila; Rose-Marie Andsten; Mikael Jumppanen; Michele Assante; Jouni Jokela; Matti Wahlsten; Kornelia M. Mikula; Cihad Sigindere; Daniel H. Kwak; Muriel Gugger; Harri Koskela; Kaarina Sivonen; Xinyu Liu; Jari Yli-Kauhaluoma; Hideo Iwaï; David P. Fewer. 2019. "Biosynthesis of the Bis-Prenylated Alkaloids Muscoride A and B." ACS Chemical Biology 14, no. 12: 2683-2690.

Journal article
Published: 09 August 2019 in FEMS Microbiology Ecology
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Heterotrophic bacteria are important drivers of nitrogen (N) cycling and the processing of dissolved organic matter (DOM). Projected increases in precipitation will potentially cause increased loads of riverine DOM to the Baltic Sea and likely affect the composition and function of bacterioplankton communities. To investigate this, the effects of riverine DOM from two different catchment areas (agricultural and forest) on natural bacterioplankton assemblages from two contrasting sites in the Baltic Sea were examined. Two microcosm experiments were carried out, where the community composition (16S rRNA gene sequencing), the composition of a suite of N-cycling genes (metagenomics) and the abundance and transcription of ammonia monooxygenase (amoA) genes involved in nitrification (quantitative PCR) were investigated. The river water treatments evoked a significant response in bacterial growth, but the effects on overall community composition and the representation of N-cycling genes were limited. Instead, treatment effects were reflected in the prevalence of specific taxonomic families, specific N-related functions and in the transcription of amoA genes. The study suggests that bacterioplankton responses to changes in the DOM pool are constrained to part of the bacterial community, whereas most taxa remain relatively unaffected.

ACS Style

Elisabeth M Happel; Trine Markussen; Jonna Teikari; Vimala Huchaiah; Johannes Alneberg; Anders F Andersson; Kaarina Sivonen; Mathias Middelboe; Veljo Kisand; Lasse Riemann. Effects of allochthonous dissolved organic matter input on microbial composition and nitrogen-cycling genes at two contrasting estuarine sites. FEMS Microbiology Ecology 2019, 95, 1 .

AMA Style

Elisabeth M Happel, Trine Markussen, Jonna Teikari, Vimala Huchaiah, Johannes Alneberg, Anders F Andersson, Kaarina Sivonen, Mathias Middelboe, Veljo Kisand, Lasse Riemann. Effects of allochthonous dissolved organic matter input on microbial composition and nitrogen-cycling genes at two contrasting estuarine sites. FEMS Microbiology Ecology. 2019; 95 (9):1.

Chicago/Turabian Style

Elisabeth M Happel; Trine Markussen; Jonna Teikari; Vimala Huchaiah; Johannes Alneberg; Anders F Andersson; Kaarina Sivonen; Mathias Middelboe; Veljo Kisand; Lasse Riemann. 2019. "Effects of allochthonous dissolved organic matter input on microbial composition and nitrogen-cycling genes at two contrasting estuarine sites." FEMS Microbiology Ecology 95, no. 9: 1.

Journal article
Published: 19 June 2019 in Biochimica et Biophysica Acta (BBA) - Biomembranes
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Hassallidins are cyclic glycolipopeptides produced by cyanobacteria and other prokaryotes. The hassallidin structure consists of a peptide ring of eight amino acids where a fatty acid chain, additional amino acid, and sugar moieties are attached. Hassallidins show antifungal activity against several opportunistic human pathogenic fungi, but does not harbor antibacterial effects. However, they have not been studied on mammalian cells, and the mechanism of action is unknown. We purified hassallidin D from cultured cyanobacterium Anabaena sp. UHCC 0258 and characterized its effect on mammalian and fungal cells. Ultrastructural analysis showed that hassallidin D disrupts cell membranes, causing a lytic/necrotic cell death with rapid presence of disintegrated outer membrane, accompanied by internalization of small molecules such as propidium iodide into the cells. Furthermore, artificial liposomal membrane assay showed that hassallidin D selectively targets sterol-containing membranes. Finally, in silico membrane modeling allowed us to study the interaction between hassallidin D and membranes in detail, and confirm the role of cholesterol for hassallidin-insertion into the membrane. This study demonstrates the mechanism of action of the natural compound hassallidin, and gives further insight into how bioactive lipopeptide metabolites selectively target eukaryotic cell membranes.

ACS Style

Anu Humisto; Jouni Jokela; Knut Teigen; Matti Wahlsten; Perttu Permi; Kaarina Sivonen; Lars Herfindal. Characterization of the interaction of the antifungal and cytotoxic cyclic glycolipopeptide hassallidin with sterol-containing lipid membranes. Biochimica et Biophysica Acta (BBA) - Biomembranes 2019, 1861, 1510 -1521.

AMA Style

Anu Humisto, Jouni Jokela, Knut Teigen, Matti Wahlsten, Perttu Permi, Kaarina Sivonen, Lars Herfindal. Characterization of the interaction of the antifungal and cytotoxic cyclic glycolipopeptide hassallidin with sterol-containing lipid membranes. Biochimica et Biophysica Acta (BBA) - Biomembranes. 2019; 1861 (8):1510-1521.

Chicago/Turabian Style

Anu Humisto; Jouni Jokela; Knut Teigen; Matti Wahlsten; Perttu Permi; Kaarina Sivonen; Lars Herfindal. 2019. "Characterization of the interaction of the antifungal and cytotoxic cyclic glycolipopeptide hassallidin with sterol-containing lipid membranes." Biochimica et Biophysica Acta (BBA) - Biomembranes 1861, no. 8: 1510-1521.

Journal article
Published: 07 May 2019 in Marine Drugs
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Microcystins are a family of chemically diverse hepatotoxins produced by distantly related cyanobacteria and are potent inhibitors of eukaryotic protein phosphatases 1 and 2A. Here we provide evidence for the biosynthesis of rare variants of microcystin that contain a selection of homo-amino acids by the benthic strain Phormidium sp. LP904c. This strain produces at least 16 microcystin chemical variants many of which contain homophenylalanine or homotyrosine. We retrieved the complete 54.2 kb microcystin (mcy) gene cluster from a draft genome assembly. Analysis of the substrate specificity of McyB1 and McyC adenylation domain binding pockets revealed divergent substrate specificity sequences, which could explain the activation of homo-amino acids which were present in 31% of the microcystins detected and included variants such as MC-LHty, MC-HphHty, MC-LHph and MC-HphHph. The mcy gene cluster did not encode enzymes for the synthesis of homo-amino acids but may instead activate homo-amino acids produced during the synthesis of anabaenopeptins. We observed the loss of microcystin during cultivation of a closely related strain, Phormidium sp. DVL1003c. This study increases the knowledge of benthic cyanobacterial strains that produce microcystin variants and broadens the structural diversity of known microcystins.

ACS Style

Tânia Keiko Shishido; Jouni Jokela; Anu Humisto; Suvi Suurnäkki; Matti Wahlsten; Danillo O. Alvarenga; Kaarina Sivonen; David P. Fewer. The Biosynthesis of Rare Homo-Amino Acid Containing Variants of Microcystin by a Benthic Cyanobacterium. Marine Drugs 2019, 17, 271 .

AMA Style

Tânia Keiko Shishido, Jouni Jokela, Anu Humisto, Suvi Suurnäkki, Matti Wahlsten, Danillo O. Alvarenga, Kaarina Sivonen, David P. Fewer. The Biosynthesis of Rare Homo-Amino Acid Containing Variants of Microcystin by a Benthic Cyanobacterium. Marine Drugs. 2019; 17 (5):271.

Chicago/Turabian Style

Tânia Keiko Shishido; Jouni Jokela; Anu Humisto; Suvi Suurnäkki; Matti Wahlsten; Danillo O. Alvarenga; Kaarina Sivonen; David P. Fewer. 2019. "The Biosynthesis of Rare Homo-Amino Acid Containing Variants of Microcystin by a Benthic Cyanobacterium." Marine Drugs 17, no. 5: 271.

Journal article
Published: 20 March 2019 in Scientific Reports
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The Baltic Sea is a shallow basin of brackish water in which the spatial salinity gradient is one of the most important factors contributing to species distribution. The Baltic Sea is infamous for its annual cyanobacterial blooms comprised of Nodularia spumigena, Aphanizomenon spp., and Dolichospermum spp. that cause harm, especially for recreational users. To broaden our knowledge of the cyanobacterial adaptation strategies for brackish water environments, we sequenced the entire genome of Dolichospermum sp. UHCC 0315, a species occurring not only in freshwater environments but also in brackish water. Comparative genomics analyses revealed a close association with Dolichospermum sp. UHCC 0090 isolated from a lake in Finland. The genome closure of Dolichospermum sp. UHCC 0315 unraveled a mixture of two subtypes in the original culture, and subtypes exhibited distinct buoyancy phenotypes. Salinity less than 3 g L-1 NaCl enabled proper growth of Dolichospermum sp. UHCC 0315, whereas growth was arrested at moderate salinity (6 g L-1 NaCl). The concentrations of toxins, microcystins, increased at moderate salinity, whereas RNA sequencing data implied that Dolichospermum remodeled its primary metabolism in unfavorable high salinity. Based on our results, the predicted salinity decrease in the Baltic Sea may favor toxic blooms of Dolichospermum spp.

ACS Style

Jonna E. Teikari; Rafael V. Popin; Shengwei Hou; Matti Wahlsten; Wolfgang Hess; Kaarina Sivonen. Insight into the genome and brackish water adaptation strategies of toxic and bloom-forming Baltic Sea Dolichospermum sp. UHCC 0315. Scientific Reports 2019, 9, 4888 .

AMA Style

Jonna E. Teikari, Rafael V. Popin, Shengwei Hou, Matti Wahlsten, Wolfgang Hess, Kaarina Sivonen. Insight into the genome and brackish water adaptation strategies of toxic and bloom-forming Baltic Sea Dolichospermum sp. UHCC 0315. Scientific Reports. 2019; 9 (1):4888.

Chicago/Turabian Style

Jonna E. Teikari; Rafael V. Popin; Shengwei Hou; Matti Wahlsten; Wolfgang Hess; Kaarina Sivonen. 2019. "Insight into the genome and brackish water adaptation strategies of toxic and bloom-forming Baltic Sea Dolichospermum sp. UHCC 0315." Scientific Reports 9, no. 1: 4888.

Journal article
Published: 15 February 2019 in Applied and Environmental Microbiology
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Herein, we deciphered the most important biosynthetic traits of a prominent group of bioactive lipopeptides. We reveal evidence for initiation of biosynthesis by two alternative starter units hardwired directly in the same gene cluster, eventually resulting in the production of a remarkable range of lipopeptide variants. We identified several unusual tailoring genes potentially involved in modifying the fatty acid chain. Careful characterization of these biosynthetic gene clusters and their diverse products could provide important insight into lipopeptide biosynthesis in prokaryotes. Some of the variants identified exhibit cytotoxic and antifungal properties, and some are associated with a toxigenic biofilm-forming strain. The findings may prove valuable to researchers in the fields of natural product discovery and toxicology.

ACS Style

Jan Mareš; Jan Hájek; Petra Urajová; Andreja Kust; Jouni Jokela; Kumar Saurav; Tomáš Galica; Kateřina Čapková; Antti Mattila; Esa Haapaniemi; Perttu Permi; Ivar Mysterud; Olav M. Skulberg; Jan Karlsen; David P. Fewer; Kaarina Sivonen; Hanne Hjorth Tønnesen; Pavel Hrouzek. Alternative Biosynthetic Starter Units Enhance the Structural Diversity of Cyanobacterial Lipopeptides. Applied and Environmental Microbiology 2019, 85, 1 .

AMA Style

Jan Mareš, Jan Hájek, Petra Urajová, Andreja Kust, Jouni Jokela, Kumar Saurav, Tomáš Galica, Kateřina Čapková, Antti Mattila, Esa Haapaniemi, Perttu Permi, Ivar Mysterud, Olav M. Skulberg, Jan Karlsen, David P. Fewer, Kaarina Sivonen, Hanne Hjorth Tønnesen, Pavel Hrouzek. Alternative Biosynthetic Starter Units Enhance the Structural Diversity of Cyanobacterial Lipopeptides. Applied and Environmental Microbiology. 2019; 85 (4):1.

Chicago/Turabian Style

Jan Mareš; Jan Hájek; Petra Urajová; Andreja Kust; Jouni Jokela; Kumar Saurav; Tomáš Galica; Kateřina Čapková; Antti Mattila; Esa Haapaniemi; Perttu Permi; Ivar Mysterud; Olav M. Skulberg; Jan Karlsen; David P. Fewer; Kaarina Sivonen; Hanne Hjorth Tønnesen; Pavel Hrouzek. 2019. "Alternative Biosynthetic Starter Units Enhance the Structural Diversity of Cyanobacterial Lipopeptides." Applied and Environmental Microbiology 85, no. 4: 1.

Research article
Published: 19 November 2018 in Biochemistry
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Aromatic prenylation is an important step in the biosynthesis of many natural products and leads to an astonishing diversity of chemical structures. Cyanobactin pathways frequently encode aromatic prenyltransferases that catalyze the prenylation of these macrocyclic and linear peptides. Here we characterized the anacyclamide (acy) biosynthetic gene cluster from Anabaena sp. UHCC-0232. Partial reconstitution of the anacyclamide pathway, heterologous expression and in vitro biochemical characterization of the enzyme demonstrate that the AcyF enzyme encoded in this biosynthetic gene cluster is a Trp N-prenyltransferase. Phylogenetic analysis suggests the monophyletic origin and rapid diversification of the cyanobactin prenyltransferase enzymes and the multiple origins of N-1 Trp prenylation in prenylated natural products. The AcyF enzyme displayed high flexibility towards a range of Trp-containing substrates and represents an interesting new tool for biocatalytic applications.

ACS Style

Luca Dalponte; Anirudra Parajuli; Ellen Younger; Antti Mattila; Jouni Jokela; Matti Wahlsten; Niina Leikoski; Kaarina Sivonen; Scott Jarmusch; Wael ElSayed Houssen; David P. Fewer. N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway. Biochemistry 2018, 57, 6860 -6867.

AMA Style

Luca Dalponte, Anirudra Parajuli, Ellen Younger, Antti Mattila, Jouni Jokela, Matti Wahlsten, Niina Leikoski, Kaarina Sivonen, Scott Jarmusch, Wael ElSayed Houssen, David P. Fewer. N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway. Biochemistry. 2018; 57 (50):6860-6867.

Chicago/Turabian Style

Luca Dalponte; Anirudra Parajuli; Ellen Younger; Antti Mattila; Jouni Jokela; Matti Wahlsten; Niina Leikoski; Kaarina Sivonen; Scott Jarmusch; Wael ElSayed Houssen; David P. Fewer. 2018. "N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway." Biochemistry 57, no. 50: 6860-6867.