Applied evolution: phylogeny-based approaches in natural products research

2019 ◽  
Vol 36 (9) ◽  
pp. 1295-1312 ◽  
Author(s):  
Martina Adamek ◽  
Mohammad Alanjary ◽  
Nadine Ziemert
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Structure Elucidation ◽  
Phylogenetic Analyses ◽  
Natural Product Discovery

Here we highlight how phylogenetic analyses can be used to facilitate natural product discovery and structure elucidation.

scholarly journals The Tripod for Bacterial Natural Product Discovery: Genome Mining, Silent Pathway Induction, and Mass Spectrometry-Based Molecular Networking

mSystems ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Daniela B. B. Trivella ◽  
Rafael de Felicio
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Natural Product ◽  
Biosynthetic Pathway ◽  
Genome Mining ◽  
Chemical Compounds ◽  
Gene Clusters ◽  
Tandem Mass ◽  
Molecular Networking ◽  
Natural Product Discovery

ABSTRACT Natural products are the richest source of chemical compounds for drug discovery. Particularly, bacterial secondary metabolites are in the spotlight due to advances in genome sequencing and mining, as well as for the potential of biosynthetic pathway manipulation to awake silent (cryptic) gene clusters under laboratory cultivation. Further progress in compound detection, such as the development of the tandem mass spectrometry (MS/MS) molecular networking approach, has contributed to the discovery of novel bacterial natural products. The latter can be applied directly to bacterial crude extracts for identifying and dereplicating known compounds, therefore assisting the prioritization of extracts containing novel natural products, for example. In our opinion, these three approaches—genome mining, silent pathway induction, and MS-based molecular networking—compose the tripod for modern bacterial natural product discovery and will be discussed in this perspective.

scholarly journals The Combination of Tradition and Future: Data-Driven Natural-Product-Based Treatments for Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhijun Miao ◽  
Jinwei Bai ◽  
Li Shen ◽  
Rajeev K. Singla
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Natural Products ◽  
Natural Product ◽  
Neurodegenerative Disorder ◽  
Data Driven ◽  
Natural Product Discovery ◽  
Challenges And Opportunities ◽  
Future Data ◽  
Personalized Diagnosis

Parkinson’s disease (PD) is a neurodegenerative disorder in elderly people. The personalized diagnosis and treatment remain challenges all over the world. In recent years, natural products are becoming potential therapies for many complex diseases due to their stability and low drug resistance. With the development of informatics technologies, data-driven natural product discovery and healthcare is becoming reality. For PD, however, the relevant research and tools for natural products are quite limited. Here in this review, we summarize current available databases, tools, and models for general natural product discovery and synthesis. These useful resources could be used and integrated for future PD-specific natural product investigations. At the same time, the challenges and opportunities for future natural-product-based PD care will also be discussed.

scholarly journals Distribution and Diversity of Natural Product Genes in Marine and Freshwater Cyanobacterial Cultures and Genomes

2005 ◽  
Vol 71 (11) ◽  
pp. 7401-7413 ◽  
Author(s):  
Ian M. Ehrenreich ◽  
John B. Waterbury ◽  
Eric A. Webb
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Phylogenetic Analyses ◽  
Molecular Data ◽  
Degenerate Primers ◽  
Molecular Systems ◽  
Peptide Synthetases ◽  
Sequence Identification ◽  
Functionally Diverse ◽  
Novel Products

ABSTRACT Natural products are a functionally diverse class of biochemically synthesized compounds, which include antibiotics, toxins, and siderophores. In this paper, we describe both the detection of natural product activities and the sequence identification of gene fragments from two molecular systems that have previously been implicated in natural product production, i.e., nonribosomal peptide synthetases (NRPSs) and modular polyketide synthases (PKSs), in diverse marine and freshwater cyanobacterial cultures. Using degenerate PCR and the sequencing of cloned products, we show that NRPSs and PKSs are common among the cyanobacteria tested. Our molecular data, when combined with genomic searches of finished and progressing cyanobacterial genomes, demonstrate that not all cyanobacteria contain NRPS and PKS genes and that the filamentous and heterocystous cyanobacteria are the richest sources of these genes and the most likely sources of novel natural products within the phylum. In addition to validating the use of degenerate primers for the identification of PKS and NRPS genes in cyanobacteria, this study also defines numerous gene fragments that will be useful as probes for future studies of the synthesis of natural products in cyanobacteria. Phylogenetic analyses of the cyanobacterial NRPS and PKS fragments sequenced in this study, as well as those from the cyanobacterial genome projects, demonstrate that there is remarkable diversity and likely novelty of these genes within the cyanobacteria. These results underscore the potential variety of novel products being produced by these ubiquitous organisms.

scholarly journals Isolation and Structure Elucidation of New Secondary Metabolites from New Zealand Marine Red Algae

2021 ◽  
Author(s):  
◽  
Wendy Lynne Popplewell
Keyword(s):  
Antibacterial Activity ◽  
Natural Products ◽  
New Zealand ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Red Algae ◽  
Structure Elucidation ◽  
Screening Tool ◽  
Product Analysis ◽  
Algal Extracts

<p>The natural product analysis of New Zealand red algae has been neglected in recent years, and there is obvious scope for the chemical re-evaluation of New Zealand marine red algae. This study describes the isolation and structure elucidation of 12 new and eight known compounds from four different genera of red algae. To aid in this process, 34 red algae were screened in order to generate a digital HSQC spectra mask, a screening tool developed by the VUW Marine Natural Products group to identify extracts of interest for further analysis. All 34 algal extracts were screened using the HSQC mask and four extracts were identified as interesting and analysed in detail. Examination of extracts of the red algae Plocamium costatum and Ballia callitricha lead to the isolation of three known metabolites. Eleven new oxylipins, labillarides A to K, are reported from the alga Phacelocarpus labillardieri. Labillarides A to H are polyunsaturated alpha-pyrone macrocycles, all of which show similarities to the previously reported compounds isolated from southern Australian collections of the algae. Labillarides E to H are of particular interest as they represent the two diastereomeric pairs associated with variation at the C-3 and C-8 chiral centres. Labillarides I and J are related enol macrocycles while labillaride K is a furan-3-one oxylipin, all of which have biogenic significance to the macrocyclic alpha-pyrones. Labillarides A, B and I exhibit moderate cytotoxicity while labillaride C shows moderate antibacterial activity. A new nitrogenous bromophenol, colensolide A, was isolated from the alga Osmundaria colensoi along with five known bromophenols. The presence of nitrogen-containing sidechains in bromophenols is unusual but not unprecedented. The bicyclic nitrogenous moiety observed in colensolide A is proposed to be of histidine origin. Several of the known bromophenols exhibit antibacterial activity and one shows moderate cytotoxicity.</p>

scholarly journals Isolation and Structure Elucidation of New Secondary Metabolites from New Zealand Marine Red Algae

2021 ◽  
Author(s):  
◽  
Wendy Lynne Popplewell
Keyword(s):  
Antibacterial Activity ◽  
Natural Products ◽  
New Zealand ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Red Algae ◽  
Structure Elucidation ◽  
Screening Tool ◽  
Product Analysis ◽  
Algal Extracts

<p>The natural product analysis of New Zealand red algae has been neglected in recent years, and there is obvious scope for the chemical re-evaluation of New Zealand marine red algae. This study describes the isolation and structure elucidation of 12 new and eight known compounds from four different genera of red algae. To aid in this process, 34 red algae were screened in order to generate a digital HSQC spectra mask, a screening tool developed by the VUW Marine Natural Products group to identify extracts of interest for further analysis. All 34 algal extracts were screened using the HSQC mask and four extracts were identified as interesting and analysed in detail. Examination of extracts of the red algae Plocamium costatum and Ballia callitricha lead to the isolation of three known metabolites. Eleven new oxylipins, labillarides A to K, are reported from the alga Phacelocarpus labillardieri. Labillarides A to H are polyunsaturated alpha-pyrone macrocycles, all of which show similarities to the previously reported compounds isolated from southern Australian collections of the algae. Labillarides E to H are of particular interest as they represent the two diastereomeric pairs associated with variation at the C-3 and C-8 chiral centres. Labillarides I and J are related enol macrocycles while labillaride K is a furan-3-one oxylipin, all of which have biogenic significance to the macrocyclic alpha-pyrones. Labillarides A, B and I exhibit moderate cytotoxicity while labillaride C shows moderate antibacterial activity. A new nitrogenous bromophenol, colensolide A, was isolated from the alga Osmundaria colensoi along with five known bromophenols. The presence of nitrogen-containing sidechains in bromophenols is unusual but not unprecedented. The bicyclic nitrogenous moiety observed in colensolide A is proposed to be of histidine origin. Several of the known bromophenols exhibit antibacterial activity and one shows moderate cytotoxicity.</p>

scholarly journals Imaging mass spectrometry for natural products discovery: a review of ionization methods

2020 ◽  
Vol 37 (2) ◽  
pp. 150-162 ◽  
Author(s):  
Joseph E. Spraker ◽  
Gordon T. Luu ◽  
Laura M. Sanchez
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Natural Product ◽  
Imaging Mass Spectrometry ◽  
Natural Product Discovery ◽  
Ionization Sources ◽  
Natural Products Discovery ◽  
Ionization Methods

This mini review discusses advantages, limitations, and examples of different mass spectrometry ionization sources applicable to natural product discovery workflows.

scholarly journals Coupling Mass Spectral and Genomic Information to Improve Bacterial Natural Product Discovery Workflows

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 142 ◽  
Author(s):  
Max Crüsemann
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Natural Product ◽  
Large Scale ◽  
Genome Mining ◽  
Structural Diversity ◽  
Gene Clusters ◽  
Genomic Information ◽  
Mass Spectral ◽  
Natural Product Discovery

Bacterial natural products possess potent bioactivities and high structural diversity and are typically encoded in biosynthetic gene clusters. Traditional natural product discovery approaches rely on UV- and bioassay-guided fractionation and are limited in terms of dereplication. Recent advances in mass spectrometry, sequencing and bioinformatics have led to large-scale accumulation of genomic and mass spectral data that is increasingly used for signature-based or correlation-based mass spectrometry genome mining approaches that enable rapid linking of metabolomic and genomic information to accelerate and rationalize natural product discovery. In this mini-review, these approaches are presented, and discovery examples provided. Finally, future opportunities and challenges for paired omics-based natural products discovery workflows are discussed.

scholarly journals Discovery of the leinamycin family of natural products by mining actinobacterial genomes

2017 ◽  
Vol 114 (52) ◽  
pp. E11131-E11140 ◽  
Author(s):  
Guohui Pan ◽  
Zhengren Xu ◽  
Zhikai Guo ◽  
Hindra ◽  
Ming Ma ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Structural Diversity ◽  
Building Blocks ◽  
Combinatorial Biosynthesis ◽  
Pathway Engineering ◽  
Natural Product Discovery ◽  
Knowledge Based ◽  
Metabolic Pathway Engineering ◽  
Strain Collection

Nature’s ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF–SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF–SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature’s rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature’s biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.

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