scholarly journals The biosynthetic diversity of the animal world

2019 ◽  
Vol 294 (46) ◽  
pp. 17684-17692 ◽  
Author(s):  
Joshua P. Torres ◽  
Eric W. Schmidt
Keyword(s):  
Dark Matter ◽  
Natural Products ◽  
Secondary Metabolites ◽  
Small Molecules ◽  
Secondary Metabolism ◽  
Symbiotic Bacteria ◽  
Biosynthetic Enzymes ◽  
Functional Roles ◽  
The Past ◽  
Plant Research

Secondary metabolites are often considered within the remit of bacterial or plant research, but animals also contain a plethora of these molecules with important functional roles. Classical feeding studies demonstrate that, whereas some are derived from diet, many of these compounds are made within the animals. In the past 15 years, the genetic and biochemical origin of several animal natural products has been traced to partnerships with symbiotic bacteria. More recently, a number of animal genome-encoded pathways to microbe-like natural products have come to light. These pathways are sometimes horizontally acquired from bacteria, but more commonly they unveil a new and diverse animal biochemistry. In this review, we highlight recent examples of characterized animal biosynthetic enzymes that reveal an unanticipated breadth and intricacy in animal secondary metabolism. The results so far suggest that there may be an immense diversity of animal small molecules and biosynthetic enzymes awaiting discovery. This biosynthetic dark matter is just beginning to be understood, providing a relatively untapped frontier for discovery.

scholarly journals Natural Products in Polyclad Flatworms

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 47
Author(s):  
Justin M. McNab ◽  
Jorge Rodríguez ◽  
Peter Karuso ◽  
Jane E. Williamson
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Marine Invertebrates ◽  
Symbiotic Bacteria ◽  
Chemical Defences ◽  
Number Of Species ◽  
Bioactive Secondary Metabolites ◽  
Potential Sources ◽  
Polyclad Flatworms

Marine invertebrates are promising sources of novel bioactive secondary metabolites, and organisms like sponges, ascidians and nudibranchs are characterised by possessing potent defensive chemicals. Animals that possess chemical defences often advertise this fact with aposematic colouration that potential predators learn to avoid. One seemingly defenceless group that can present bright colouration patterns are flatworms of the order Polycladida. Although members of this group have typically been overlooked due to their solitary and benthic nature, recent studies have isolated the neurotoxin tetrodotoxin from these mesopredators. This review considers the potential of polyclads as potential sources of natural products and reviews what is known of the activity of the molecules found in these animals. Considering the ecology and diversity of polyclads, only a small number of species from both suborders of Polycladida, Acotylea and Cotylea have been investigated for natural products. As such, confirming assumptions as to which species are in any sense toxic or if the compounds they use are biosynthesised, accumulated from food or the product of symbiotic bacteria is difficult. However, further research into the group is suggested as these animals often display aposematic colouration and are known to prey on invertebrates rich in bioactive secondary metabolites.

scholarly journals Bioactive Secondary Metabolites of the Genus Diaporthe and Anamorph Phomopsis from Terrestrial and Marine Habitats and Endophytes: 2010–2019

2021 ◽  
Vol 9 (2) ◽  
pp. 217
Author(s):  
Tang-Chang Xu ◽  
Yi-Han Lu ◽  
Jun-Fei Wang ◽  
Zhi-Qiang Song ◽  
Ya-Ge Hou ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Small Molecules ◽  
Host Plants ◽  
Plant Pathogens ◽  
Bioactive Metabolites ◽  
Drug Candidates ◽  
The Past ◽  
Marine Habitats ◽  
Bioactive Secondary Metabolites ◽  
Unidentified Species

The genus Diaporthe and its anamorph Phomopsis are distributed worldwide in many ecosystems. They are regarded as potential sources for producing diverse bioactive metabolites. Most species are attributed to plant pathogens, non-pathogenic endophytes, or saprobes in terrestrial host plants. They colonize in the early parasitic tissue of plants, provide a variety of nutrients in the cycle of parasitism and saprophytism, and participate in the basic metabolic process of plants. In the past ten years, many studies have been focused on the discovery of new species and biological secondary metabolites from this genus. In this review, we summarize a total of 335 bioactive secondary metabolites isolated from 26 known species and various unidentified species of Diaporthe and Phomopsis during 2010–2019. Overall, there are 106 bioactive compounds derived from Diaporthe and 246 from Phomopsis, while 17 compounds are found in both of them. They are classified into polyketides, terpenoids, steroids, macrolides, ten-membered lactones, alkaloids, flavonoids, and fatty acids. Polyketides constitute the main chemical population, accounting for 64%. Meanwhile, their bioactivities mainly involve cytotoxic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, anti-algae, phytotoxic, and enzyme inhibitory activities. Diaporthe and Phomopsis exhibit their potent talents in the discovery of small molecules for drug candidates.

scholarly journals Unlocking Fungal Cryptic Natural Products

2009 ◽  
Vol 4 (11) ◽  
pp. 1934578X0900401 ◽  
Author(s):  
Yi-Ming Chiang ◽  
Kuan-Han Lee ◽  
James F. Sanchez ◽  
Nancy P. Keller ◽  
Clay C. C. Wang
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Analytical Methods ◽  
State Of The Art ◽  
Molecular Genetic ◽  
Biosynthetic Pathways ◽  
Fungal Metabolites ◽  
Potential Sources ◽  
Fungal Genomes

Recent published sequencing of fungal genomes has revealed that these microorganisms have a surprisingly large number of secondary metabolite pathways that can serve as potential sources for new and useful natural products. Most of the secondary metabolites and their biosynthesis pathways are currently unknown, possibly because they are produced in very small amounts and are thus difficult to detect or are produced only under specific conditions. Elucidating these fungal metabolites will require new molecular genetic tools, better understanding of the regulation of secondary metabolism, and state of the art analytical methods. This review describes recent strategies to mine the cryptic natural products and their biosynthetic pathways in fungi.

scholarly journals A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones

2021 ◽  
Vol 22 (5) ◽  
pp. 2769
Author(s):  
Joonseong Hur ◽  
Jaebong Jang ◽  
Jaehoon Sim
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Small Molecules ◽  
Biologically Active ◽  
Synthetic Methods ◽  
Pharmacological Activities ◽  
New Developments ◽  
The Past ◽  
Privileged Structures ◽  
Significant Attention

γ-Butyrolactone, a five-membered lactone moiety, is one of the privileged structures of diverse natural products and biologically active small molecules. Because of their broad spectrum of biological and pharmacological activities, synthetic methods for γ-butyrolactones have received significant attention from synthetic and medicinal chemists for decades. Recently, new developments and improvements in traditional methods have been reported by considering synthetic efficiency, feasibility, and green chemistry. In this review, the pharmacological activities of natural and synthetic γ-butyrolactones are described, including their structures and bioassay methods. Mainly, we summarize recent advances, occurring during the past decade, in the construction of γ-butyrolactone classified based on the bond formation in γ-butyrolactone between (i) C5-O1 bond, (ii) C4-C5 and C2-O1 bonds, (iii) C3-C4 and C2-O1 bonds, (iv) C3-C4 and C5-O1 bonds, (v) C2-C3 and C2-O1 bonds, (vi) C3-C4 bond, and (vii) C2-O1 bond. In addition, the application to the total synthesis of natural products bearing γ-butyrolactone scaffolds is described.

scholarly journals Secondary metabolism in the gill microbiota of shipworms (Teredinidae) as revealed by comparison of metagenomes and nearly complete symbiont genomes

2019 ◽  
Author(s):  
Marvin A. Altamia ◽  
Zhenjian Lin ◽  
Amaro E. Trindade-Silva ◽  
Iris Diana Uy ◽  
J. Reuben Shipway ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Gene Clusters ◽  
The United States ◽  
Biosynthetic Gene Cluster ◽  
The Philippines ◽  
Symbiotic Bacteria ◽  
Biosynthetic Pathways ◽  
Biosynthetic Gene ◽  
Bioactive Secondary Metabolites

AbstractShipworms play critical roles in recycling wood in the sea. Symbiotic bacteria supply enzymes that the organisms need for nutrition and wood degradation. Some of these bacteria have been grown in pure culture and have the capacity to make many secondary metabolites. However, little is known about whether such secondary metabolite pathways are represented in the symbiont communities within their hosts. In addition, little has been reported about the patterns of host-symbiont co-occurrence. Here, we collected shipworms from the United States, the Philippines, and Brazil, and cultivated symbiotic bacteria from their gills. We analyzed sequences from 22 shipworm gill metagenomes from seven shipworm species and from 23 cultivated symbiont isolates. Using (meta)genome sequencing, we demonstrate that the cultivated isolates represent all the major bacterial symbiont species and strains in shipworm gills. We show that the bacterial symbionts are distributed among shipworm hosts in consistent, predictable patterns. The symbiotic bacteria encode many biosynthetic gene cluster families (GCFs) for bioactive secondary metabolites, only <5% of which match previously described biosynthetic pathways. Because we were able to cultivate the symbionts, and sequence their genomes, we can definitively enumerate the biosynthetic pathways in these symbiont communities, showing that ∼150 out of ∼200 total biosynthetic gene clusters (BGCs) present in the animal gill metagenomes are represented in our culture collection. Shipworm symbionts occur in suites that differ predictably across a wide taxonomic and geographic range of host species, and collectively constitute an immense resource for the discovery of new biosynthetic pathways to bioactive secondary metabolites.ImportanceWe define a system in which the major symbionts that are important to host biology and to the production of secondary metabolites can be cultivated. We show that symbiotic bacteria that are critical to host nutrition and lifestyle also have an immense capacity to produce a multitude of diverse and likely novel bioactive secondary metabolites that could lead to the discovery of drugs, and that these pathways are found within shipworm gills. We propose that, by shaping associated microbial communities within the host, the compounds support the ability of shipworms to degrade wood in marine environments. Because these symbionts can be cultivated and genetically manipulated, they provide a powerful model for understanding how secondary metabolism impacts microbial symbiosis.

scholarly journals Secondary Metabolism in the Gill Microbiota of Shipworms (Teredinidae) as Revealed by Comparison of Metagenomes and Nearly Complete Symbiont Genomes

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Marvin A. Altamia ◽  
Zhenjian Lin ◽  
Amaro E. Trindade-Silva ◽  
Iris Diana Uy ◽  
J. Reuben Shipway ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Gene Clusters ◽  
The United States ◽  
The Philippines ◽  
Culture Collection ◽  
Symbiotic Bacteria ◽  
Biosynthetic Pathways ◽  
Bioactive Secondary Metabolites ◽  
Genetically Manipulated

ABSTRACT Shipworms play critical roles in recycling wood in the sea. Symbiotic bacteria supply enzymes that the organisms need for nutrition and wood degradation. Some of these bacteria have been grown in pure culture and have the capacity to make many secondary metabolites. However, little is known about whether such secondary metabolite pathways are represented in the symbiont communities within their hosts. In addition, little has been reported about the patterns of host-symbiont co-occurrence. Here, we collected shipworms from the United States, the Philippines, and Brazil and cultivated symbiotic bacteria from their gills. We analyzed sequences from 22 shipworm gill metagenomes from seven shipworm species and from 23 cultivated symbiont isolates. Using (meta)genome sequencing, we demonstrate that the cultivated isolates represent all the major bacterial symbiont species and strains in shipworm gills. We show that the bacterial symbionts are distributed among shipworm hosts in consistent, predictable patterns. The symbiotic bacteria harbor many gene cluster families (GCFs) for biosynthesis of bioactive secondary metabolites, only <5% of which match previously described biosynthetic pathways. Because we were able to cultivate the symbionts and to sequence their genomes, we can definitively enumerate the biosynthetic pathways in these symbiont communities, showing that ∼150 of ∼200 total biosynthetic gene clusters (BGCs) present in the animal gill metagenomes are represented in our culture collection. Shipworm symbionts occur in suites that differ predictably across a wide taxonomic and geographic range of host species and collectively constitute an immense resource for the discovery of new biosynthetic pathways corresponding to bioactive secondary metabolites. IMPORTANCE We define a system in which the major symbionts that are important to host biology and to the production of secondary metabolites can be cultivated. We show that symbiotic bacteria that are critical to host nutrition and lifestyle also have an immense capacity to produce a multitude of diverse and likely novel bioactive secondary metabolites that could lead to the discovery of drugs and that these pathways are found within shipworm gills. We propose that, by shaping associated microbial communities within the host, the compounds support the ability of shipworms to degrade wood in marine environments. Because these symbionts can be cultivated and genetically manipulated, they provide a powerful model for understanding how secondary metabolism impacts microbial symbiosis.

scholarly journals Engineering biosynthetic enzymes for industrial natural product synthesis

2020 ◽  
Vol 37 (8) ◽  
pp. 1122-1143 ◽  
Author(s):  
Stephanie Galanie ◽  
David Entwistle ◽  
James Lalonde
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Secondary Metabolism ◽  
Natural Product Synthesis ◽  
Biosynthetic Enzymes ◽  
Metabolism Enzymes ◽  
Industrial Relevance

This review describes examples of the broadening industrial relevance of engineered secondary metabolism enzymes, natural products and analogs being made with these enzymes, and technology improvements that have enabled their development since 1999.

scholarly journals Integration of Plasma Membrane and Nuclear Signaling in Elicitor Regulation of Plant Secondary Metabolism

2008 ◽  
Vol 3 (8) ◽  
pp. 1934578X0800300
Author(s):  
Gastón Stockman ◽  
Ricardo Boland
Keyword(s):  
Natural Products ◽  
Transcriptional Regulation ◽  
Plasma Membrane ◽  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Biosynthetic Pathways ◽  
Plant Secondary Metabolism ◽  
Design Strategies ◽  
Nuclear Signaling ◽  
Physical Changes

The plant kingdom represents a valuable source of natural products of commercial interest. These compounds, named secondary metabolites, are not essential for the survival of plants, but confer them some advantages that allow adaptation to changes in their environment. Nevertheless, yields of secondary metabolites are low for commercial purposes, so it has become important to design strategies for increasing their production. Plants manage to adapt to physical changes in their environment, defending themselves against pathogen attack or herbivore wounding. Such aggressive stimuli, also known as elicitors, initiate signaling metabolic cascades that induce accumulation of certain secondary metabolites. Progress has been recently achieved in the understanding of signaling events originating from elicitation and related transcriptional regulation. These advances will allow maneuvering expression of key enzymes implicated in biosynthetic pathways of secondary metabolites, thereby enhancing their accumulation.

scholarly journals Natural Products from Nocardia and Their Role in Pathogenicity

2021 ◽  
pp. 1-16
Author(s):  
Alicia Engelbrecht ◽  
Hamada Saad ◽  
Harald Gross ◽  
Leonard Kaysser
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Small Molecules ◽  
Genome Sequencing ◽  
Immune Evasion ◽  
Environmental Conditions ◽  
Human Host ◽  
Metal Chelating ◽  
Systemic Infections

<i>Nocardia</i> spp. are filamentous Actinobacteria of the order Corynebacteriales and mostly known for their ability to cause localized and systemic infections in humans. However, the onset and progression of nocardiosis is only poorly understood, in particular the mechanisms of strain-specific presentations. Recent genome sequencing has revealed an extraordinary capacity for the production of specialized small molecules. Such secondary metabolites are often crucial for the producing microbe to survive the challenges of different environmental conditions. An interesting question thus concerns the role of these natural products in <i>Nocardia-</i>associated pathogenicity and immune evasion in a human host. In this review, a summary and discussion of <i>Nocardia</i> metabolites is presented, which may play a part in nocardiosis because of their cytotoxic, immunosuppressive and metal-chelating properties or otherwise vitally important functions. This review also contains so far unpublished data concerning the biosynthesis of these molecules that were obtained by detailed bioinformatic analyses.

scholarly journals Spatial Molecular Architecture of the Microbial Community of a Peltigera Lichen

mSystems ◽  
2016 ◽  
Vol 1 (6) ◽  
Author(s):  
Neha Garg ◽  
Yi Zeng ◽  
Anna Edlund ◽  
Alexey V. Melnik ◽  
Laura M. Sanchez ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Small Molecules ◽  
Gene Clusters ◽  
Chemical Components ◽  
Organic Chemical ◽  
Metagenomic Sequencing ◽  
Biosynthetic Gene Clusters ◽  
Functional Roles ◽  
Fungal Natural Products

ABSTRACT Microbial communities have evolved over centuries to live symbiotically. The direct visualization of such communities at the chemical and functional level presents a challenge. Overcoming this challenge may allow one to visualize the spatial distributions of specific molecules involved in symbiosis and to define their functional roles in shaping the community structure. In this study, we examined the diversity of microbial genes and taxa and the presence of biosynthetic gene clusters by metagenomic sequencing and the compartmentalization of organic chemical components within a lichen using mass spectrometry. This approach allowed the identification of chemically distinct sections within this composite organism. Using our multipronged approach, various fungal natural products, not previously reported from lichens, were identified and two different fungal layers were visualized at the chemical level. Microbes are commonly studied as individual species, but they exist as mixed assemblages in nature. At present, we know very little about the spatial organization of the molecules, including natural products that are produced within these microbial networks. Lichens represent a particularly specialized type of symbiotic microbial assemblage in which the component microorganisms exist together. These composite microbial assemblages are typically comprised of several types of microorganisms representing phylogenetically diverse life forms, including fungi, photosymbionts, bacteria, and other microbes. Here, we employed matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) imaging mass spectrometry to characterize the distributions of small molecules within a Peltigera lichen. In order to probe how small molecules are organized and localized within the microbial consortium, analytes were annotated and assigned to their respective producer microorganisms using mass spectrometry-based molecular networking and metagenome sequencing. The spatial analysis of the molecules not only reveals an ordered layering of molecules within the lichen but also supports the compartmentalization of unique functions attributed to various layers. These functions include chemical defense (e.g., antibiotics), light-harvesting functions associated with the cyanobacterial outer layer (e.g., chlorophyll), energy transfer (e.g., sugars) surrounding the sun-exposed cyanobacterial layer, and carbohydrates that may serve a structural or storage function and are observed with higher intensities in the non-sun-exposed areas (e.g., complex carbohydrates). IMPORTANCE Microbial communities have evolved over centuries to live symbiotically. The direct visualization of such communities at the chemical and functional level presents a challenge. Overcoming this challenge may allow one to visualize the spatial distributions of specific molecules involved in symbiosis and to define their functional roles in shaping the community structure. In this study, we examined the diversity of microbial genes and taxa and the presence of biosynthetic gene clusters by metagenomic sequencing and the compartmentalization of organic chemical components within a lichen using mass spectrometry. This approach allowed the identification of chemically distinct sections within this composite organism. Using our multipronged approach, various fungal natural products, not previously reported from lichens, were identified and two different fungal layers were visualized at the chemical level.

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