Dataset Information

RBAN: retro-biosynthetic analysis of nonribosomal peptides.

ABSTRACT: Proteinogenic and non-proteinogenic amino acids, fatty acids or glycans are some of the main building blocks of nonribsosomal peptides (NRPs) and as such may give insight into the origin, biosynthesis and bioactivities of their constitutive peptides. Hence, the structural representation of NRPs using monomers provides a biologically interesting skeleton of these secondary metabolites. Databases dedicated to NRPs such as Norine, already integrate monomer-based annotations in order to facilitate the development of structural analysis tools. In this paper, we present rBAN (retro-biosynthetic analysis of nonribosomal peptides), a new computational tool designed to predict the monomeric graph of NRPs from their atomic structure in SMILES format. This prediction is achieved through the "in silico" fragmentation of a chemical structure and matching the resulting fragments against the monomers of Norine for identification. Structures containing monomers not yet recorded in Norine, are processed in a "discovery mode" that uses the RESTful service from PubChem to search the unidentified substructures and suggest new monomers. rBAN was integrated in a pipeline for the curation of Norine data in which it was used to check the correspondence between the monomeric graphs annotated in Norine and SMILES-predicted graphs. The process concluded with the validation of the 97.26% of the records in Norine, a two-fold extension of its SMILES data and the introduction of 11 new monomers suggested in the discovery mode. The accuracy, robustness and high-performance of rBAN were demonstrated in benchmarking it against other tools with the same functionality: Smiles2Monomers and GRAPE.

SUBMITTER: Ricart E

PROVIDER: S-EPMC6689883 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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rBAN: retro-biosynthetic analysis of nonribosomal peptides.

Ricart Emma E Leclère Valérie V Flissi Areski A Mueller Markus M Pupin Maude M Lisacek Frédérique F

Journal of cheminformatics 20190208 1

Proteinogenic and non-proteinogenic amino acids, fatty acids or glycans are some of the main building blocks of nonribsosomal peptides (NRPs) and as such may give insight into the origin, biosynthesis and bioactivities of their constitutive peptides. Hence, the structural representation of NRPs using monomers provides a biologically interesting skeleton of these secondary metabolites. Databases dedicated to NRPs such as Norine, already integrate monomer-based annotations in order to facilitate t ...[more]

PMID: 30737579

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Project description:Natural and non-natural cyclic peptides are a crucial component in drug discovery programs because of their considerable pharmaceutical properties. Cyclosporin, microcystins, and nodularins are all notable pharmacologically important cyclic peptides. Because these biologically active peptides are often biosynthesized nonribosomally, they often contain nonstandard amino acids, thus increasing the complexity of the resulting tandem mass spectrometry data. In addition, because of the cyclic nature, the fragmentation patterns of many of these peptides showed much higher complexity when compared to related counterparts. Therefore, at the present time it is still difficult to annotate cyclic peptides MS/MS spectra. In this current work, an annotation program was developed for the annotation and characterization of tandem mass spectra obtained from cyclic peptides. This program, which we call MS-CPA is available as a web tool (http://lol.ucsd.edu/ms-cpa_v1/Input.py). Using this program, we have successfully annotated the sequence of representative cyclic peptides, such as seglitide, tyrothricin, desmethoxymajusculamide C, dudawalamide A, and cyclomarins, in a rapid manner and also were able to provide the first-pass structure evidence of a newly discovered natural product based on predicted sequence. This compound is not available in sufficient quantities for structural elucidation by other means such as NMR. In addition to the development of this cyclic annotation program, it was observed that some cyclic peptides fragmented in unexpected ways resulting in the scrambling of sequences. In summary, MS-CPA not only provides a platform for rapid confirmation and annotation of tandem mass spectrometry data obtained with cyclic peptides but also enables quantitative analysis of the ion intensities. This program facilitates cyclic peptide analysis, sequencing, and also acts as a useful tool to investigate the uncommon fragmentation phenomena of cyclic peptides and aids the characterization of newly discovered cyclic peptides encountered in drug discovery programs.

Dataset Information

RBAN: retro-biosynthetic analysis of nonribosomal peptides.

Publications

rBAN: retro-biosynthetic analysis of nonribosomal peptides.

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