scholarly journals Mining Natural Product Biosynthesis in Eukaryotic Algae

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 90
Author(s):  
Ellis O’Neill
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Harmful Algal Blooms ◽  
Algal Blooms ◽  
Gene Clusters ◽  
Future Research ◽  
Eukaryotic Algae ◽  
Cyclic Polyethers ◽  
Automated Tools ◽  
Bacteria And Fungi

Eukaryotic algae are an extremely diverse category of photosynthetic organisms and some species produce highly potent bioactive compounds poisonous to humans or other animals, most notably observed during harmful algal blooms. These natural products include some of the most poisonous small molecules known and unique cyclic polyethers. However, the diversity and complexity of algal genomes means that sequencing-based research has lagged behind research into more readily sequenced microbes, such as bacteria and fungi. Applying informatics techniques to the algal genomes that are now available reveals new natural product biosynthetic pathways, with different groups of algae containing different types of pathways. There is some evidence for gene clusters and the biosynthetic logic of polyketides enables some prediction of these final products. For other pathways, it is much more challenging to predict the products and there may be many gene clusters that are not identified with the automated tools. These results suggest that there is a great diversity of biosynthetic capacity for natural products encoded in the genomes of algae and suggest areas for future research focus.

scholarly journals CuAAC click chemistry for the enhanced detection of novel alkyne-based natural product toxins

2018 ◽  
Vol 54 (86) ◽  
pp. 12234-12237 ◽  
Author(s):  
Edward S. Hems ◽  
Ben A. Wagstaff ◽  
Gerhard Saalbach ◽  
Robert A. Field
Keyword(s):  
Natural Products ◽  
Click Chemistry ◽  
Natural Product ◽  
Harmful Algal Blooms ◽  
Algal Blooms ◽  
Terminal Alkyne

In the context of discovering and quantifying terminal alkyne-based natural products, here we report the combination of CuAAC click chemistry with LC-MS for the detection of polyether toxins (prymnesins) associated with harmful algal blooms.

scholarly journals Synthetic Biology Advanced Natural Product Discovery

Metabolites ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 785
Author(s):  
Junyang Wang ◽  
Jens Nielsen ◽  
Zihe Liu
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Natural Product ◽  
Rapid Development ◽  
Genome Mining ◽  
Gene Clusters ◽  
Future Research ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Natural Product Discovery

A wide variety of bacteria, fungi and plants can produce bioactive secondary metabolites, which are often referred to as natural products. With the rapid development of DNA sequencing technology and bioinformatics, a large number of putative biosynthetic gene clusters have been reported. However, only a limited number of natural products have been discovered, as most biosynthetic gene clusters are not expressed or are expressed at extremely low levels under conventional laboratory conditions. With the rapid development of synthetic biology, advanced genome mining and engineering strategies have been reported and they provide new opportunities for discovery of natural products. This review discusses advances in recent years that can accelerate the design, build, test, and learn (DBTL) cycle of natural product discovery, and prospects trends and key challenges for future research directions.

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 Challenges and Advances in Genome Editing Technologies in Streptomyces

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 734 ◽  
Author(s):  
Yawei Zhao ◽  
Guoquan Li ◽  
Yunliang Chen ◽  
Yinhua Lu
Keyword(s):  
Natural Product ◽  
Genome Editing ◽  
Genetic Manipulation ◽  
Chemical Compounds ◽  
Gene Clusters ◽  
Future Research ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Research Focus ◽  
Experimental Conditions

The genome of Streptomyces encodes a high number of natural product (NP) biosynthetic gene clusters (BGCs). Most of these BGCs are not expressed or are poorly expressed (commonly called silent BGCs) under traditional laboratory experimental conditions. These NP BGCs represent an unexplored rich reservoir of natural compounds, which can be used to discover novel chemical compounds. To activate silent BGCs for NP discovery, two main strategies, including the induction of BGCs expression in native hosts and heterologous expression of BGCs in surrogate Streptomyces hosts, have been adopted, which normally requires genetic manipulation. So far, various genome editing technologies have been developed, which has markedly facilitated the activation of BGCs and NP overproduction in their native hosts, as well as in heterologous Streptomyces hosts. In this review, we summarize the challenges and recent advances in genome editing tools for Streptomyces genetic manipulation with a focus on editing tools based on clustered regularly interspaced short palindrome repeat (CRISPR)/CRISPR-associated protein (Cas) systems. Additionally, we discuss the future research focus, especially the development of endogenous CRISPR/Cas-based genome editing technologies in Streptomyces.

Genome-Guided Discovery of Natural Products and Biosynthetic Pathways from Australia’s Untapped Microbial Megadiversity

2016 ◽  
Vol 69 (2) ◽  
pp. 129 ◽  
Author(s):  
John A. Kalaitzis ◽  
Shane D. Ingrey ◽  
Rocky Chau ◽  
Yvette Simon ◽  
Brett A. Neilan
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Genome Sequencing ◽  
Dna Sequences ◽  
Gene Clusters ◽  
Biosynthetic Pathways ◽  
Natural Product Biosynthesis ◽  
Guided Discovery ◽  
Biosynthesis Gene ◽  
Microbial Natural Products

Historically microbial natural product biosynthesis pathways were elucidated mainly by isotope labelled precursor directed feeding studies. Now the genetics underpinning the assembly of microbial natural products biosynthesis is so well understood that some pathways and their products can be predicted from DNA sequences alone. The association between microbial natural products and their biosynthesis gene clusters is now driving the field of ‘genetics guided natural product discovery’. This account overviews our research into cyanotoxin biosynthesis before the genome sequencing era through to some recent discoveries resulting from the mining of Australian biota for natural product biosynthesis pathways.

scholarly journals Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

2015 ◽  
Vol 81 (13) ◽  
pp. 4339-4350 ◽  
Author(s):  
Qi Zhang ◽  
James R. Doroghazi ◽  
Xiling Zhao ◽  
Mark C. Walker ◽  
Wilfred A. van der Donk
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Gene Cluster ◽  
Posttranslational Modifications ◽  
Large Scale ◽  
Biological Activities ◽  
Gene Clusters ◽  
Chemical Diversity ◽  
Content Type ◽  
Modified Peptides

ABSTRACTLanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Lanthipeptides are widely distributed in taxonomically distant species, and their currently known biosynthetic systems and biological activities are diverse. Building on the recent natural product gene cluster family (GCF) project, we report here large-scale analysis of lanthipeptide-like biosynthetic gene clusters fromActinobacteria. Our analysis suggests that lanthipeptide biosynthetic pathways, and by extrapolation the natural products themselves, are much more diverse than currently appreciated and contain many different posttranslational modifications. Furthermore, lanthionine synthetases are much more diverse in sequence and domain topology than currently characterized systems, and they are used by the biosynthetic machineries for natural products other than lanthipeptides. The gene cluster families described here significantly expand the chemical diversity and biosynthetic repertoire of lanthionine-related natural products. Biosynthesis of these novel natural products likely involves unusual and unprecedented biochemistries, as illustrated by several examples discussed in this study. In addition, class IV lanthipeptide gene clusters are shown not to be silent, setting the stage to investigate their biological activities.

scholarly journals A Scientometric Overview of Global Dinoflagellate Research

Publications ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 50
Author(s):  
Carlos Yure B. Oliveira ◽  
Cicero Diogo L. Oliveira ◽  
Marius N. Müller ◽  
Elizabeth P. Santos ◽  
Danielli M. M. Dantas ◽  
...  
Keyword(s):  
Harmful Algal Blooms ◽  
Algal Blooms ◽  
Research Output ◽  
Research Field ◽  
Future Research ◽  
Scientometric Analysis ◽  
Fish Production ◽  
Emerging Trends ◽  
Basic Characteristics ◽  
Number Of Publications

Understanding the evolution of scientific literature is a critical and necessary step for the development and strengthening of a research field. However, an overview of global dinoflagellate research remains unavailable. Herein, global dinoflagellate research output was analyzed based on a scientometric approach using the Scopus data archive. The basic characteristics and worldwide interactions of dinoflagellate research output were analyzed to determine the temporal evolution and new emerging trends. The results confirm that dinoflagellate research output, reflected in the number of publications, is a fast-growing area since the mid-1990s. In total, five research subareas emerged using a bibliometric keywords analysis: (1) “symbiosis with coral reefs”, (2) “phylogeny”, (3) “palynology”, (4) “harmful algal blooms” and (5) “nutrition strategies”. Dinoflagellate publications were modeled by fish production (both aquaculture and fisheries) and economic and social indexes. Finally, directions for future research are proposed and discussed. The presented scientometric analysis confirms that dinoflagellate research is an active and important area with focus on mitigating economic impacts, especially in regard to fish production.

scholarly journals Natural Product Gene Clusters in the Filamentous Nostocales Cyanobacterium HT-58-2

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 356
Author(s):  
Xiaohe Jin ◽  
Eric S. Miller ◽  
Jonathan S. Lindsey
Keyword(s):  
Natural Products ◽  
Nitrogen Fixation ◽  
Natural Product ◽  
Microbial Consortium ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Nitrogen Stress ◽  
Biosynthetic Gene ◽  
Tetrapyrrole Biosynthesis ◽  
The Rich

Cyanobacteria are known as rich repositories of natural products. One cyanobacterial-microbial consortium (isolate HT-58-2) is known to produce two fundamentally new classes of natural products: the tetrapyrrole pigments tolyporphins A–R, and the diterpenoid compounds tolypodiol, 6-deoxytolypodiol, and 11-hydroxytolypodiol. The genome (7.85 Mbp) of the Nostocales cyanobacterium HT-58-2 was annotated previously for tetrapyrrole biosynthesis genes, which led to the identification of a putative biosynthetic gene cluster (BGC) for tolyporphins. Here, bioinformatics tools have been employed to annotate the genome more broadly in an effort to identify pathways for the biosynthesis of tolypodiols as well as other natural products. A putative BGC (15 genes) for tolypodiols has been identified. Four BGCs have been identified for the biosynthesis of other natural products. Two BGCs related to nitrogen fixation may be relevant, given the association of nitrogen stress with production of tolyporphins. The results point to the rich biosynthetic capacity of the HT-58-2 cyanobacterium beyond the production of tolyporphins and tolypodiols.

scholarly journals A Multi-Omics Characterization of the Natural Product Potential of Tropical Filamentous Marine Cyanobacteria

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 20
Author(s):  
Tiago Leão ◽  
Mingxun Wang ◽  
Nathan Moss ◽  
Ricardo da Silva ◽  
Jon Sanders ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Genome Mining ◽  
Gene Clusters ◽  
Microbial Interactions ◽  
Marine Cyanobacteria ◽  
Pharmaceutical Drugs ◽  
Genes Encoding ◽  
Microbial Natural Products

Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples.

scholarly journals Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lanthipeptides

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3001026
Author(s):  
Alexander M. Kloosterman ◽  
Peter Cimermancic ◽  
Somayah S. Elsayed ◽  
Chao Du ◽  
Michalis Hadjithomas ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Sequence Similarity ◽  
Genome Mining ◽  
Gene Clusters ◽  
Support Vector ◽  
Chemical Labeling ◽  
Product Families ◽  
Anticancer Properties ◽  
Modified Peptides

Microbial natural products constitute a wide variety of chemical compounds, many which can have antibiotic, antiviral, or anticancer properties that make them interesting for clinical purposes. Natural product classes include polyketides (PKs), nonribosomal peptides (NRPs), and ribosomally synthesized and post-translationally modified peptides (RiPPs). While variants of biosynthetic gene clusters (BGCs) for known classes of natural products are easy to identify in genome sequences, BGCs for new compound classes escape attention. In particular, evidence is accumulating that for RiPPs, subclasses known thus far may only represent the tip of an iceberg. Here, we present decRiPPter (Data-driven Exploratory Class-independent RiPP TrackER), a RiPP genome mining algorithm aimed at the discovery of novel RiPP classes. DecRiPPter combines a Support Vector Machine (SVM) that identifies candidate RiPP precursors with pan-genomic analyses to identify which of these are encoded within operon-like structures that are part of the accessory genome of a genus. Subsequently, it prioritizes such regions based on the presence of new enzymology and based on patterns of gene cluster and precursor peptide conservation across species. We then applied decRiPPter to mine 1,295 Streptomyces genomes, which led to the identification of 42 new candidate RiPP families that could not be found by existing programs. One of these was studied further and elucidated as a representative of a novel subfamily of lanthipeptides, which we designate class V. The 2D structure of the new RiPP, which we name pristinin A3 (1), was solved using nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS) data, and chemical labeling. Two previously unidentified modifying enzymes are proposed to create the hallmark lanthionine bridges. Taken together, our work highlights how novel natural product families can be discovered by methods going beyond sequence similarity searches to integrate multiple pathway discovery criteria.

Sign in / Sign up

Export Citation Format

Share Document