Dereplication: racing to speed up the natural products discovery process

Abstract

Covering: 1993-2014 (July)To alleviate the dereplication holdup, which is a major bottleneck in natural products discovery, scientists have been conducting their research efforts to add tools to their "bag of tricks" aiming to achieve faster, more accurate and efficient ways to accelerate the pace of the drug discovery process. Consequently dereplication has become a hot topic presenting a huge publication boom since 2012, blending multidisciplinary fields in new ways that provide important conceptual and/or methodological advances, opening up pioneering research prospects in this field.

Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules

“…This decision might have been premature, not only because restocking our antibiotic supplies is a public health priority, but also because modern advances in genome sequencing technologies and the development of bioinformatics have reinvigorated antibiotic discovery. The abundance of bacterial genome sequences now available enables genome-mining approaches for finding new bioactive small molecules, while simultaneously facilitating cheminformatic dereplication methods (Gaudêncio and Pereira 2015;Mohamed, Nguyen and Mamitsuka 2016).…”

New Dereplication Method Applied to NMR-Based Metabolomics on DifferentFusariumSpecies Isolated from Rhizosphere ofSenna spectabilis

“…1,2 Classic dereplication methods use biological screening processes followed by databases queries in order to evaluate the data obtained on the state of the art technologies and hyphenated protocols, such as liquid chromatography coupled to a diode array detector with high-resolution mass spectrometry (LC-DAD-HRMS) and LC-DAD-NMR (nuclear magnetic resonance), LC-DAD-MS/MS (tandem mass spectrometry). [4][5][6][7][8] More recently, several other tools have been developed, aiming to achieve efficient and more factual paths for metabolite elucidation through analysis of high-resolution metabolite profiling. 7 Among the enhancements in the dereplication process, we highlight 2D 13 C NMR, high throughput screening (HTS), bioinformatics, MS/MS molecular networking applied to the omics sciences (genomics, proteomics, metabolomics), as well as chemometrics and other statistical tools, such as partial least-square discriminant analysis (PLS-DA), statistical total correlation spectroscopy (STOCSY).…”

“…[4][5][6][7][8] More recently, several other tools have been developed, aiming to achieve efficient and more factual paths for metabolite elucidation through analysis of high-resolution metabolite profiling. 7 Among the enhancements in the dereplication process, we highlight 2D 13 C NMR, high throughput screening (HTS), bioinformatics, MS/MS molecular networking applied to the omics sciences (genomics, proteomics, metabolomics), as well as chemometrics and other statistical tools, such as partial least-square discriminant analysis (PLS-DA), statistical total correlation spectroscopy (STOCSY). 6,7,[9][10][11] In parallel to the development of new dereplication tools, microorganisms, especially those isolated from unstudied NP matrices, such as plant's rhizosphere and marine organisms, appear as an interesting source of new active compounds, mainly due to their high molecular complexity and potential to produce heterogeneous secondary metabolites.…”

“…7 Among the enhancements in the dereplication process, we highlight 2D 13 C NMR, high throughput screening (HTS), bioinformatics, MS/MS molecular networking applied to the omics sciences (genomics, proteomics, metabolomics), as well as chemometrics and other statistical tools, such as partial least-square discriminant analysis (PLS-DA), statistical total correlation spectroscopy (STOCSY). 6,7,[9][10][11] In parallel to the development of new dereplication tools, microorganisms, especially those isolated from unstudied NP matrices, such as plant's rhizosphere and marine organisms, appear as an interesting source of new active compounds, mainly due to their high molecular complexity and potential to produce heterogeneous secondary metabolites. 12,13 Furthermore, microbes also possess the ability to use different solid substrates as a result of their biochemistry and biological evolution, enabling the survival in different environments through mutualistic association with plants and other organisms, allowing the production of different active metabolites in a single strain.…”

Pufferfish mortality associated with novel polar marine toxins in Hawaii

“…That highly polar toxins are problematic to purify and detect is reflected in the marine toxin literature where they comprise a minority (< 5%) of documented natural toxins (Blunt et al 2012). If we are to truly understand the role of marine toxins in wildlife mortalities (and human health), we will need a more efficient way to identify novel compounds (Gaudencio & Pereira 2015).…”