Impact of domestication in the production of the class II lanthipeptide lichenicidin by bacillus licheniformis I89

Investigation on lantibiotics biosynthesis constitutes an emergent field, since these molecules have demonstrated a great potential to replace the so-called ‘‘traditional antibiotics’’. The adaptation of bacteria to laboratory conditions (domestication) is an unpredictable phenomenon, which sometimes is associated with the loss of important biotechnological properties. In this study, the domestication of Bacillus licheniformis was associated with the production of the lantibiotic lichenicidin, a twopeptide lantibiotic with activity against several Grampositive bacteria

Mass spectrometry guided venom profiling and bioactivity screening of the Anatolian Meadow Viper, Vipera anatolica

WOS: 000366539600002PubMed ID: 26385313This contribution reports on the first characterization of the venom proteome and the bioactivity screening of Vipera anatolica, the Anatolian Meadow Viper. The crude venom as well as an isolated dimeric disintegrin showed remarkable cytotoxic activity against glioblastoma cells. Due to the rare occurrence and the small size of this species only little amount of venom was available, which was profiled by means of a combination of bottom-up and top-down mass spectrometry. From this analysis we identified snake venom metalloproteases, cysteine-rich secretory protein isoforms, a metalloprotease inhibitor, several type A2 phospholipases, disintegrins, a snake venom serine protease, a C-type lectin and a Kunitz-type protease inhibitor. Furthermore, we detected several isoforms of above mentioned proteins as well as previously unknown proteins, indicating an extensive complexity of the venom which would have remained undetected with conventional venomic approaches. (C) 2015 Elsevier Ltd. All rights reserved.Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG); Scientific and Technical Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111T338]; Cluster of Excellence Unifying Concepts in Catalysis (UniCat)German Research Foundation (DFG)This study was supported by the Deutsche Forschungsgemeinschaft (DFG), Cluster of Excellence Unifying Concepts in Catalysis (UniCat) and by the Scientific and Technical Research Council of Turkey (TUBITAK) under Grant 111T338. We thank Dr. Rashed Al Toma and Eric van Herwerden (TU Berlin) for helpful discussion on the manuscript as well as Mert Karis M. Anil Oguz and Volkan Eroglu (Ege University, Izmir) for field assistances. We also thank to AREL (Ege University School of Medicine Research and Education Laboratory) for the permission to use their laboratory

Highlighting the possible secondary interactions in the role of balhimycin and its analogues for enantiorecognition in capillary electrophoresis

It is believed that the enantiorecognition mechanism based on macrocyclic antibiotics involves multi-modal interactions via hydrogen bonding. pi-pi interaction, steric hindrance, hydrophobic interaction and so on. A variety of enantiomeric N-benzoylated amino acids were separated using balhimycin (A) or its analogues bromobalhimycin (B) and dechlorobalhimycin (C) as chiral mobile phase additive using a CE method, which combined the partial filling technique with the dynamic coating technique and the co-EOF electrophoresis technique. The enantioresolution and the migration time were highly relevant to the structure of analytes, especially to the substitutions on the N-tagged benzoyl moiety of the amino acids. A steric effect and pi-pi interaction based mechanism is proposed in order to explain some observed enantioresolution differences between positional isomers. Notably dechlorobalhimycin exhibited the best enantioresolution for several N-benzoylated derivatives of leucine, which was rarely observed for N-dansylated amino acid derivatives. The hydrophobicity difference of the aglycone pocket among three chiral selectors was assumed to account for this behaviour. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved

Investigating the cytotoxic effects of the venom proteome of two species of the Viperidae family (Cerastes cerastes and Cryptelytrops purpureomaculatus) from various habitats

WOS: 000469306000003PubMed ID: 30825636Animal secretions are of great interest in terms of drug development due to their complex protein and peptide composition. Especially, in the field of therapeutic medications such as anti-cancer drugs snake venoms receive attention. In this study, we address two Viperidae species from various habitats with a particular focus on the cytotoxic potential along with the decomplexation of the venom proteome: the horned desert viper (Cerastes cerastes), native to desert regions of North Africa and the mangrove pit viper (Cryptelytrops purpureomaculatus), found in coastal forests of Southeast Asia. Initial cytotoxic screenings of the crude venoms revealed diverse activity, with the highest effect against SHSY5Y human glioblastoma carcinoma cells compared to other cancerous and non-cancerous cell lines. In-depth cytotoxicity studies of SHSY5Y cells with purified venom fractions revealed heterodimeric disintegrins from C. cerastes venom, which exerted a high cytotoxic activity with IC50 values from 0.11 to 0.58 mu M and a disintegrin-like effect on SHSY5Y morphology was observed due to cell detachment. Furthermore, two polyproline BPP-related peptides, one PLA(2) and a peptide-rich fraction were determined for C. purpureomaculatus with moderate IC50 values between 3 and 51 mu M. Additionally, the decryption of the venom proteomes by snake venomic mass spectrometry and comparison of the same species from different habitats revealed slight differences in the composition

Silvalactam, a 24-membered macrolactam antibiotic produced by Streptomyces sp Tu 6392

Streptomycetes were isolated out of a soil sample taken from the rhizosphere of a spruce stand and screened by HPLC-diode array analysis for the production of secondary metabolites. This led to the detection of silvalactam, a novel 24-membered macrolactam antibiotic in extracts of Streptomyces strain Tu 6392. The structure was determined by MS and NMR spectroscopy experiments. Silvalactam shows a potent antiproliferative activity against various cancerous and non-cancerous cell lines. The Journal of Antibiotics (2012) 65, 369-372; doi: 10.1038/ja.2012.33; published online 9 May 201

Comparative Venomics of the Vipera ammodytes transcaucasiana and Vipera ammodytes montandoni from Turkey Provides Insights into Kinship

WOS: 000424096500023PubMed ID: 29301241The Nose-horned Viper (Vipera ammodytes) is one of the most widespread and venomous snakes in Europe, which causes high frequent snakebite accidents. The first comprehensive venom characterization of the regional endemic Transcaucasian Nose-horned Viper (Vipera ammodytes transcaucasiana) and the Transdanubian Sand Viper (Vipera ammodytes montandoni) is reported employing a combination of intact mass profiling and bottom-up proteomics. The bottom-up analysis of both subspecies identified the major snake protein families of viper venoms. Furthermore, intact mass profiling revealed the presence of two tripeptidic metalloprotease inhibitors and their precursors. While previous reports applied multivariate analysis techniques to clarify the taxonomic status of the subspecies, an accurate classification of Vipera ammodytestranscaucasiana is still part of the ongoing research. The comparative analysis of the viper venoms on the proteome level reveals a close relationship between the Vipera ammodytes subspecies, which could be considered to clarify the classification of the Transcaucasian Nose-horned Viper. However, the slightly different ratio of some venom components could be indicating interspecific variations of the two studied subspecies or intraspecies alternations based on small sample size. Additionally, we performed a bioactivity screening with the crude venoms against several human cancerous and non-cancerous cell lines, which showed interesting results against a human breast adenocarcinoma epithelial cell line. Several fractions of Vipera a. transcaucasiana demonstrated a strong cytotoxic effect on triple negative MDA MB 231 breast cancer cells.German Research FoundationGerman Research Foundation (DFG); Technische Universitat BerlinWe thank Daniel Petras (University of California) and Rashed Al Toma (TU Berlin) for helpful discussion on the manuscript. We acknowledge support by the German Research Foundation and the Open Access Publication Funds of Technische Universitat Berlin