scholarly journals Recent developments of tools for genome and metabolome studies in basidiomycete fungi and their application to natural product research

Biology Open ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. bio056010
Author(s):  
Fabrizio Alberti ◽  
Saraa Kaleem ◽  
Jack A. Weaver
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Gene Clusters ◽  
Bioactive Metabolites ◽  
Network Analyses ◽  
Natural Product Research ◽  
Technological Advances ◽  
Long Read ◽  
Recent Developments ◽  
Basidiomycete Fungi

ABSTRACTBasidiomycota are a large and diverse phylum of fungi. They can make bioactive metabolites that are used or have inspired the synthesis of antibiotics and agrochemicals. Terpenoids are the most abundant class of natural products encountered in this taxon. Other natural product classes have been described, including polyketides, peptides, and indole alkaloids. The discovery and study of natural products made by basidiomycete fungi has so far been hampered by several factors, which include their slow growth and complex genome architecture. Recent developments of tools for genome and metabolome studies are allowing researchers to more easily tackle the secondary metabolome of basidiomycete fungi. Inexpensive long-read whole-genome sequencing enables the assembly of high-quality genomes, improving the scaffold upon which natural product gene clusters can be predicted. CRISPR/Cas9-based engineering of basidiomycete fungi has been described and will have an important role in linking natural products to their genetic determinants. Platforms for the heterologous expression of basidiomycete genes and gene clusters have been developed, enabling natural product biosynthesis studies. Molecular network analyses and publicly available natural product databases facilitate data dereplication and natural product characterisation. These technological advances combined are prompting a revived interest in natural product discovery from basidiomycete fungi.This article has an associated Future Leader to Watch interview with the first author of the paper.

scholarly journals Advances in Biosynthesis of Natural Products from Marine Microorganisms

2021 ◽  
Vol 9 (12) ◽  
pp. 2551
Author(s):  
Quan Zhou ◽  
Kinya Hotta ◽  
Yaming Deng ◽  
Rui Yuan ◽  
Shu Quan ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Marine Natural Products ◽  
Biological Activities ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Marine Natural Product ◽  
Marine Microorganisms ◽  
Natural Product Research ◽  
Recent Developments

Natural products play an important role in drug development, among which marine natural products are an underexplored resource. This review summarizes recent developments in marine natural product research, with an emphasis on compound discovery and production methods. Traditionally, novel compounds with useful biological activities have been identified through the chromatographic separation of crude extracts. New genome sequencing and bioinformatics technologies have enabled the identification of natural product biosynthetic gene clusters in marine microbes that are difficult to culture. Subsequently, heterologous expression and combinatorial biosynthesis have been used to produce natural products and their analogs. This review examines recent examples of such new strategies and technologies for the development of marine natural products.

scholarly journals Future Leader to Watch – Fabrizio Alberti

Biology Open ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. bio057679
Keyword(s):  
Natural Product ◽  
Life Sciences ◽  
Early Career ◽  
Early Career Researchers ◽  
Natural Product Research ◽  
Senior Research Fellow ◽  
Recent Developments ◽  
Senior Research ◽  
Selection Of ◽  
Basidiomycete Fungi

ABSTRACTFuture Leader to Watch is a series of interviews with the first authors of a selection of Reviews published in Biology Open, helping early-career researchers promote themselves alongside their papers. Fabrizio Alberti is first author on ‘Recent developments of tools for genome and metabolome studies in basidiomycete fungi and their application to natural product research’, published in BiO. Fabrizio is a Leverhulme Trust Early Career Fellow (Senior Research Fellow) at the School of Life Sciences and Department of Chemistry, University of Warwick, UK, investigating the discovery and biosynthetic characterisation of natural products made by fungi and bacteria.

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 A practical guide for transparent reporting of research on natural products in the British Journal of Pharmacology : Reproducibility of natural product research

2020 ◽  
Vol 177 (10) ◽  
pp. 2169-2178 ◽  
Author(s):  
Angelo A. Izzo ◽  
Mauro Teixeira ◽  
Steve P.H. Alexander ◽  
Giuseppe Cirino ◽  
James R. Docherty ◽  
...  
Keyword(s):  
Natural Products ◽  
British Journal ◽  
Natural Product ◽  
Practical Guide ◽  
Transparent Reporting ◽  
Natural Product Research

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 Ecopharmacognosy: Exploring The Chemical And Biological Potential Of Nature For Human Health

2014 ◽  
Vol 3 (1) ◽  
pp. 1 ◽  
Author(s):  
Geoffrey A. Cordell
Keyword(s):  
Health Care ◽  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Developed Countries ◽  
Biologically Active ◽  
Minor Role ◽  
Natural Product Research ◽  
Biological Potential ◽  
The World

“Why didn’t they develop natural product drugs in a sustainable manner at the beginning of this century?”  In 2035, when about 10.0 billion will inhabit Earth, will this be our legacy as the world contemplates the costs and availability of synthetic and gene-based products for primary health care?  Acknowledging the recent history of the relationship between humankind and the Earth, it is essential that the health care issues being left for our descendants be considered in terms of resources. For most people in the world, there are two vast health care “gaps”, access to quality drugs and the development of drugs for major global and local diseases.  Consequently for all of these people, plants, in their various forms, remain a primary source of health care.  In the developed countries, natural products derived from plants assume a relatively minor role in health care, as prescription and over-the-counter products, even with the widespread use of phytotherapeutical preparations.  Significantly, pharmaceutical companies have retrenched substantially in their disease areas of focus.  These research areas do not include the prevalent diseases of the middle- and lower-income countries, and important diseases of the developed world, such as drug resistance. What then is the vision for natural product research to maintain the choices of drug discovery and pharmaceutical development for future generations?  In this discussion some facets of how natural products must be involved globally, in a sustainable manner, for improving health care will be examined within the framework of the new term “ecopharmacognosy”, which invokes sustainability as the basis for research on biologically active natural products.  Access to the biome, the acquisition, analysis and dissemination of plant knowledge, natural product structure diversification, biotechnology development, strategies for natural product drug discovery, and aspects of multitarget therapy and synergy research will be discussed.  Options for the future will be presented which may be significant as countries decide how to develop approaches to relieve their own disease burden, and the needs of their population for improved access to medicinal agents.

scholarly journals Development of an agar-plug cultivation system for bioactivity assays of actinomycete strain collections

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258934
Author(s):  
Nico Ortlieb ◽  
Elke Klenk ◽  
Andreas Kulik ◽  
Timo Horst Johannes Niedermeyer
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Microtiter Plate ◽  
Growth Media ◽  
Natural Product Research ◽  
Solid Media ◽  
Agar Plug ◽  
Strain Collection ◽  
Actinomycete Strain ◽  
Initial Medium

Natural products are an important source of lead compounds for the development of drug substances. Actinomycetes have been valuable especially for the discovery of antibiotics. Increasing occurrence of antibiotic resistance among bacterial pathogens has revived the interest in actinomycete natural product research. Actinobacteria produce a different set of natural products when cultivated on solid growth media compared with submersed culture. Bioactivity assays involving solid media (e.g. agar-plug assays) require manual manipulation of the strains and agar plugs. This is less convenient for the screening of larger strain collections of several hundred or thousand strains. Thus, the aim of this study was to develop a 96-well microplate-based system suitable for the screening of actinomycete strain collections in agar-plug assays. We developed a medium-throughput cultivation and agar-plug assay workflow that allows the convenient inoculation of solid agar plugs with actinomycete spore suspensions from a strain collection, and the transfer of the agar plugs to petri dishes to conduct agar-plug bioactivity assays. The development steps as well as the challenges that were overcome during the development (e.g. system sterility, handling of the agar plugs) are described. We present the results from one exemplary screening campaign targeted to identify compounds inhibiting Agr-based quorum sensing where the workflow was used successfully. We present a novel and convenient workflow to combine agar diffusion assays with microtiter-plate-based cultivation systems in which strains can grow on a solid surface. This workflow facilitates and speeds up the initial medium throughput screening of natural product-producing actinomycete strain collections against monitor strains in agar-plug assays.

scholarly journals Type S Non Ribosomal Peptide Synthetases for the rapid generation of tailor-made peptide libraries

2021 ◽  
Author(s):  
Nadya Abbood ◽  
Tien Duy Vo ◽  
Jonas Watzel ◽  
Kenan A. J. Bozhueyuek ◽  
Helge B. Bode
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
De Novo ◽  
Chemical Space ◽  
Biologically Relevant ◽  
Peptide Synthetases ◽  
Medical Needs ◽  
Natural Product Research ◽  
Rapid Generation ◽  
Traditional Natural

Bacterial natural products in general, and non-ribosomally synthesized peptides in particular, are structurally diverse and provide us with a broad range of pharmaceutically relevant bioactivities. Yet, traditional natural product research suffers from rediscovering the same scaffolds and has been stigmatised as inefficient, time-, labour-, and cost-intensive. Combinatorial chemistry, on the other hand, can produce new molecules in greater numbers, cheaper and in less time than traditional natural product discovery, but also fails to meet current medical needs due to the limited biologically relevant chemical space that can be addressed. Consequently, methods for the high throughput generation of new-to-nature natural products would offer a new approach to identifying novel bioactive chemical entities for the hit to lead phase of drug discovery programms. As a follow-up to our previously published proof-of-principle study on generating bipartite type S non-ribosomal peptide synthetases (NRPSs), we now envisaged the de novo generation of non-ribosomal peptides (NRPs) on an unreached scale. Using synthetic zippers, we split NRPS in up to three subunits and rapidly generated different bi- and tripartite NRPS libraries to produce 49 peptides, peptide derivatives, and de novo peptides at good titres up to 145 mgL-1. A further advantage of type S NRPSs not only is the possibility to easily expand the created libraries by re-using previously created type S NRPS, but that functions of individual domains as well as domain-domain interactions can be studied and assigned rapidly.

A Recent Look into Natural Products that have Potential to Inhibit Cholinesterases and Monoamine Oxidase B: Update for 2010-2019

2020 ◽  
Vol 23 (9) ◽  
pp. 862-876
Author(s):  
Hayrettin O. Gulcan ◽  
Ilkay E. Orhan
Keyword(s):  
Natural Products ◽  
Monoamine Oxidase ◽  
Natural Product ◽  
Biological Activities ◽  
Treatment Options ◽  
Monoamine Oxidase B ◽  
Chemical Structures ◽  
Natural Agents ◽  
Natural Product Research ◽  
Multiple Receptors

With respect to the unknowns of pathophysiology of Alzheimer’s Disease (AD)-, and Parkinson’s Disease (PD)-like neurodegenerative disorders, natural product research is still one of the valid tools in order to provide alternative and/or better treatment options. At one hand, various extracts of herbals provide a combination of actions targeting multiple receptors, on the other hand, the discovery of active natural products (i.e., secondary metabolites) generally offers alternative chemical structures either ready to be employed in clinical studies or available to be utilized as important scaffolds for the design of novel agents. Regarding the importance of certain enzymes (e.g. cholinesterase and monoamine oxidase B), for the treatment of AD and PD, we have surveyed the natural product research within this area in the last decade. Particularly novel natural agents discovered within this period, concomitant to novel biological activities displayed for known natural products, are harmonized within the present study.

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