Depsipeptide Intermediates Interrogate Proposed Biosynthesis of Cereulide, the Emetic Toxin of Bacillus cereus. 2015

Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
Chair of Food Chemistry and Molecular Sensory Science, Technische Universität München, Lise-Meitner-Straße 34, Freising, 85354, Germany.

Cereulide and isocereulides A-G are biosynthesized as emetic toxins by Bacillus cereus via a non-ribosomal peptide synthetase (NRPS) called Ces. Although a thiotemplate mechanisms involving cyclo-trimerization of ready-made D-O-Leu-D-Ala-L-O-Val-L-Val via a thioesterase (TE) domain is proposed for cereulide biosynthesis, the exact mechanism is far from being understood. UPLC-TOF MS analysis of B. cereus strains in combination with (13)C-labeling experiments now revealed tetra-, octa-, and dodecapeptides of a different sequence, namely (L-O-Val-L-Val-D-O-Leu-D-Ala)1-3, as intermediates of cereulide biosynthesis. Surprisingly, also di-, hexa-, and decadepsipeptides were identified which, together with the structures of the previously reported isocereulides E, F, and G, do not correlate to the currently proposed mechanism for cereulide biosynthesis and violate the canonical NRPS biosynthetic logic. UPLC-TOF MS metabolite analysis and bioinformatic gene cluster analysis highlighted dipeptides rather than single amino or hydroxy acids as the basic modules in tetradepsipeptide assembly and proposed the CesA C-terminal C* domain and the CesB C-terminal TE domain to function as a cooperative esterification and depsipeptide elongation center repeatedly recruiting the action of the C* domain to oligomerize tetradepsipeptides prior to the release of cereulide from the TE domain by macrocyclization.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010453 Peptide Synthases Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups. Peptide Synthetases,Acid-Amino-Acid Ligases,Acid Amino Acid Ligases,Ligases, Acid-Amino-Acid,Synthases, Peptide,Synthetases, Peptide
D002247 Carbon Isotopes Stable carbon atoms that have the same atomic number as the element carbon but differ in atomic weight. C-13 is a stable carbon isotope. Carbon Isotope,Isotope, Carbon,Isotopes, Carbon
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003500 Cyclization Changing an open-chain hydrocarbon to a closed ring. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Cyclizations
D005810 Multigene Family A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed) Gene Clusters,Genes, Reiterated,Cluster, Gene,Clusters, Gene,Families, Multigene,Family, Multigene,Gene Cluster,Gene, Reiterated,Multigene Families,Reiterated Gene,Reiterated Genes
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001409 Bacillus cereus A species of rod-shaped bacteria that is a common soil saprophyte. Its spores are widespread and multiplication has been observed chiefly in foods. Contamination may lead to food poisoning.
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D016415 Sequence Alignment The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms. Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations

Related Publications

Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
May 2008, Letters in applied microbiology,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
February 2002, International journal of food microbiology,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
June 1995, FEMS microbiology letters,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
January 2012, Biocontrol science,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
April 2011, Applied and environmental microbiology,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
February 2021, Toxins,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
February 2011, Applied and environmental microbiology,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
May 2002, Applied and environmental microbiology,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
April 2011, Applied and environmental microbiology,
Sandra Marxen, and Timo D Stark, and Andrea Rütschle, and Genia Lücking, and Elrike Frenzel, and Siegfried Scherer, and Monika Ehling-Schulz, and Thomas Hofmann
February 2024, International journal of food microbiology,
Copied contents to your clipboard!