Impact of temperature on the biosynthesis of cytotoxically active carbamidocyclophanes A–E in Nostoc sp. CAVN10

Preisitsch, Michael; Bui, Ha Thi Ngoc; Bäcker, Christian; Mundt, S.

doi:10.1007/s10811-015-0657-7

Cited by 4 publications

(12 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CAVN2 and the cyanobacterial growth. In contrast to most of the above-mentioned studies, stock cultures, routinely grown in chlorine-containing BG-11 (≈ 0.5 mM Clˉ) [ 37 ] or modified WC (MBL) (≈ 0.5 mM Clˉ) [ 7 ] medium, were transferred to low-level halogen-containing Z½ medium (<0.1 µM halide ions, Table S1 ) and were subjected to multiple cultivation dilution until halogenated [7.7]paracyclophanes were only detectable in traces by HPLC-UV-MS analysis. Subsequently, potassium salts of chlorine, bromine, iodine, and fluorine were added to the culture broth to give a concentration of either 0.001, 0.01, 0.1, or 1.0%.…”

Section: Resultsmentioning

confidence: 99%

“…Cultivation was performed at 25 °C, i.e. , at a temperature that leads to an optimal ratio between biomass production and carbamidocyclophane content [ 37 ]. Generally, lower halide salt concentrations did not influence cyanobacterial growth over 20, 25, and 30 days of cultivation.…”

Section: Resultsmentioning

confidence: 99%

“…As depicted in Figure 6 , however, compound contents in KCl-enriched medium showed an up to 1.9-fold decrease on day 30 compared to day 24 or day 36, similar as previously seen for the quantification of carbamidocyclophanes A−E in Nostoc sp. CAVN10 biomass [ 37 ]. This was not observed for the KBr-enriched samples.…”

Section: Resultsmentioning

confidence: 99%

“…Growth was determined by measuring the dry weights. The deduced growth curves were the basis for the calculation of maximum specific growth rate ( µ max ) [ 37 ]. For compound analysis, a 10.0 mg biomass aliquot was subjected to the above-mentioned one-step biomass extraction and [7.7]paracyclophane enrichment procedure [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Effects of Halide Ions on the Carbamidocyclophane Biosynthesis in Nostoc sp. CAVN2

et al. 2016

Self Cite

View full text Add to dashboard Cite

In this study, the influence of halide ions on [7.7]paracyclophane biosynthesis in the cyanobacterium Nostoc sp. CAVN2 was investigated. In contrast to KI and KF, supplementation of the culture medium with KCl or KBr resulted not only in an increase of growth but also in an up-regulation of carbamidocyclophane production. LC-MS analysis indicated the presence of chlorinated, brominated, but also non-halogenated derivatives. In addition to 22 known cylindrocyclophanes and carbamidocyclophanes, 27 putative congeners have been detected. Nine compounds, carbamidocyclophanes M−U, were isolated, and their structural elucidation by 1D and 2D NMR experiments in combination with HRMS and ECD analysis revealed that they are brominated analogues of chlorinated carbamidocyclophanes. Quantification of the carbamidocyclophanes showed that chloride is the preferably utilized halide, but incorporation is reduced in the presence of bromide. Evaluation of the antibacterial activity of 30 [7.7]paracyclophanes and related derivatives against selected pathogenic Gram-positive and Gram-negative bacteria exhibited remarkable effects especially against methicillin- and vancomycin-resistant staphylococci and Mycobacterium tuberculosis. For deeper insights into the mechanisms of biosynthesis, the carbamidocyclophane biosynthetic gene cluster in Nostoc sp. CAVN2 was studied. The gene putatively coding for the carbamoyltransferase has been identified. Based on bioinformatic analyses, a possible biosynthetic assembly is discussed.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Halide Ions on the Carbamidocyclophane Biosynthesis in Nostoc sp. CAVN2

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Different research groups have investigated the impact of cyanobacterial culture conditions with various endpoints: to increase biomass and lipid content for biofuel production (Tedesco and Duerr 1989; Silva et al 2014; Johnson et al 2016), to analyze the release of harmful toxins (Patterson and Bolis 1993; Rapala et al 1993; Patterson and Bolis 1995; Yin et al 1997; Mazur-Marzec et al 2005; Rohrlack and Utkilen 2007; Vico et al 2016; Mowe et al 2016), to investigate the ecology and physiology of strains related to harmful algal blooms (Yue et al 2015; Briand et al 2016), to study and to improve production of useful compounds (Hong and Lee 2008) and specific bioactive molecules (Ray and Bagchi 2002; Repka et al 2004; Tarko et al 2012; Preisitsch et al 2016b; Preisitsch et al 2016a). Some of the parameters analyzed and optimized in these studies were light, temperature, pH, metals, halide ions, nitrogen source, nitrogen level, phosphate, and calcium levels.…”

Section: Introductionmentioning

confidence: 99%

The impact of culture conditions on growth and metabolomic profiles of freshwater cyanobacteria

2017

View full text Add to dashboard Cite

Cultured cyanobacteria produce secondary metabolites with a wide range of biological activities and are an important source of natural products. In the context of secondary metabolite discovery, microbial culture conditions are expected to support optimum growth, induce maximum chemical diversity, and be suitable for the majority of cyanobacterial strains. We investigated the effect of nitrate and phosphate on biomass production and metabolomic profiles of three filamentous freshwater cyanobacterial strains: cf. Oscillatoria sp. UIC 10045, Scytonema sp. UIC 10036, and Nostoc sp. UIC 10110. A standardized inoculation procedure allowed for the assessment of cell mass production. Dried cyanobacterial cell mass was extracted and analyzed by liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS), followed by comparative metabolomics analysis using XCMS Online. Results showed that low nitrate media significantly reduced cell mass production for all three strains. Low nitrate also induced production of primary metabolites (heterocyst glycolipids) in strains UIC 10036 and UIC 10110. Changes in phosphate levels affected each strain differently. Strain UIC 10110 showed a significant increase in production of merocyclophane C when cultivated in low phosphate, while strain UIC 10036 displayed higher production of tolytoxin under high phosphate. Additionally, these experiments led to the identification of a potentially new peptide produced by strain UIC 10036.

show abstract

Cylindrofridins A–C, Linear Cylindrocyclophane-Related Alkylresorcinols from the Cyanobacterium Cylindrospermum stagnale

et al. 2015

Self Cite

View full text Add to dashboard Cite

A rapid and exhaustive one-step biomass extraction as well as an enrichment and cleanup procedure has been developed for HPLC-UV detection and quantification of closely related [7.7]paracyclophanes and structural derivatives based on a two-phase solvent system. The procedure has been validated using the biomass of the carbamidocyclophane- and cylindrocyclophane-producing cyanobacterium Nostoc sp. CAVN2 and was utilized to perform a screening comprising 102 cyanobacterial strains. As a result, three new cylindrocyclophane-related alkylresorcinols, cylindrofridins A-C (1-3), and known cylindrocyclophanes (4-6) were detected and isolated from Cylindrospermum stagnale PCC 7417. Structures of 1-3 were elucidated by a combination of 1D and 2D NMR experiments, HRMS, and ECD spectroscopy. Cylindrofridin A (1) is the first naturally occurring [7.7]paracyclophane-related monomeric derivative. In contrast, cylindrofridins B (2) and C (3) represent dimers related to 1. Due to chlorination at the alkyl carbon atom in 1-3, the site of [7.7]paracyclophane macrocycle formation, the cylindrofridins represent linearized congeners of the cylindrocyclophanes. Compounds 1-3 were not toxic against nontumorigenic HaCaT cells (IC50 values >25 μM) compared to the respective cylindrocyclophanes, but 1 was the only cylindrofridin showing moderate activity against methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae with MIC values of 9 and 17 μM, respectively.

show abstract

Impact of temperature on the biosynthesis of cytotoxically active carbamidocyclophanes A–E in Nostoc sp. CAVN10

Cited by 4 publications

References 84 publications

Effects of Halide Ions on the Carbamidocyclophane Biosynthesis in Nostoc sp. CAVN2

Effects of Halide Ions on the Carbamidocyclophane Biosynthesis in Nostoc sp. CAVN2

The impact of culture conditions on growth and metabolomic profiles of freshwater cyanobacteria

Cylindrofridins A–C, Linear Cylindrocyclophane-Related Alkylresorcinols from the Cyanobacterium Cylindrospermum stagnale

Contact Info

Product

Resources

About