scholarly journals Extending the “One Strain Many Compounds” (OSMAC) Principle to Marine Microorganisms

Marine Drugs ◽  
2018 ◽  
Vol 16 (7) ◽  
pp. 244 ◽  
Author(s):  
Stefano Romano ◽  
Stephen Jackson ◽  
Sloane Patry ◽  
Alan Dobson

Genomic data often highlights an inconsistency between the number of gene clusters identified using bioinformatic approaches as potentially producing secondary metabolites and the actual number of chemically characterized secondary metabolites produced by any given microorganism. Such gene clusters are generally considered as “silent”, meaning that they are not expressed under laboratory conditions. Triggering expression of these “silent” clusters could result in unlocking the chemical diversity they control, allowing the discovery of novel molecules of both medical and biotechnological interest. Therefore, both genetic and cultivation-based techniques have been developed aimed at stimulating expression of these “silent” genes. The principles behind the cultivation based approaches have been conceptualized in the “one strain many compounds” (OSMAC) framework, which underlines how a single strain can produce different molecules when grown under different environmental conditions. Parameters such as, nutrient content, temperature, and rate of aeration can be easily changed, altering the global physiology of a microbial strain and in turn significantly affecting its secondary metabolism. As a direct extension of such approaches, co-cultivation strategies and the addition of chemical elicitors have also been used as cues to activate “silent” clusters. In this review, we aim to provide a focused and comprehensive overview of these strategies as they pertain to marine microbes. Moreover, we underline how changes in some parameters which have provided important results in terrestrial microbes, but which have rarely been considered in marine microorganisms, may represent additional strategies to awaken “silent” gene clusters in marine microbes. Unfortunately, the empirical nature of the OSMAC approach forces scientists to perform extensive laboratory experiments. Nevertheless, we believe that some computation and experimental based techniques which are used in other disciplines, and which we discuss; could be effectively employed to help streamline the OSMAC based approaches. We believe that natural products discovery in marine microorganisms would be greatly aided through the integration of basic microbiological approaches, computational methods, and technological innovations, thereby helping unearth much of the as yet untapped potential of these microorganisms.

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Zachary Charlop-Powers ◽  
Jeremy G Owen ◽  
Boojala Vijay B Reddy ◽  
Melinda A Ternei ◽  
Denise O Guimarães ◽  
...  

Recent bacterial (meta)genome sequencing efforts suggest the existence of an enormous untapped reservoir of natural-product-encoding biosynthetic gene clusters in the environment. Here we use the pyro-sequencing of PCR amplicons derived from both nonribosomal peptide adenylation domains and polyketide ketosynthase domains to compare biosynthetic diversity in soil microbiomes from around the globe. We see large differences in domain populations from all except the most proximal and biome-similar samples, suggesting that most microbiomes will encode largely distinct collections of bacterial secondary metabolites. Our data indicate a correlation between two factors, geographic distance and biome-type, and the biosynthetic diversity found in soil environments. By assigning reads to known gene clusters we identify hotspots of biomedically relevant biosynthetic diversity. These observations not only provide new insights into the natural world, they also provide a road map for guiding future natural products discovery efforts.


2020 ◽  
Vol 8 (12) ◽  
pp. 1897
Author(s):  
Shraddha Shitut ◽  
Güniz Özer Bergman ◽  
Alexander Kros ◽  
Daniel E. Rozen ◽  
Dennis Claessen

Filamentous actinobacteria are widely used as microbial cell factories to produce valuable secondary metabolites, including the vast majority of clinically relevant antimicrobial compounds. Secondary metabolites are typically encoded by large biosynthetic gene clusters, which allow for a modular approach to generating diverse compounds through recombination. Protoplast fusion is a popular method for whole genome recombination that uses fusion of cells that are transiently wall-deficient. This process has been applied for both inter- and intraspecies recombination. An important limiting step in obtaining diverse recombinants from fused protoplasts is regeneration of the cell wall, because this forces the chromosomes from different parental lines to segregate, thereby preventing further recombination. Recently, several labs have gained insight into wall-deficient bacteria that have the ability to proliferate without their cell wall, known as L-forms. Unlike protoplasts, L-forms can stably maintain multiple chromosomes over many division cycles. Fusion of such L-forms would potentially allow cells to express genes from both parental genomes while also extending the time for recombination, both of which can contribute to an increased chemical diversity. Here, we present a perspective on how L-form fusion has the potential to become a platform for novel compound discovery and may thus help to overcome the antibiotic discovery void.


Genome ◽  
2020 ◽  
Author(s):  
Yaru Gao ◽  
Xinyang Du ◽  
Huanhuan Li ◽  
Ying Wang

Due to the specific properties of the marine environment, marine microorganisms have exclusive physicochemical characteristics that are different from those of terrestrial microorganisms, which can produce various secondary metabolites (SMs) with considerable structural diversity and biological activity. In this study, three strains of coepiphytic Aspergillus with potential antibacterial activities, A7 (Aspergillus flavus), B27 (Aspergillus flavipes) and R12 (Aspergillus sydowii), were isolated from the South China Sea. Via the Illumina MiSeq sequencing platform, the genomes of the three strains were sequenced, and genome comparison showed the highest diversity of the biosynthetic gene clusters (BGCs) in A7. Meanwhile, a comparison of physiological and genomic characteristics between A7 and other Aspergillus flavus strains demonstrated the superior environmental adaptability of A7, which is apparently consistent with the genetic richness of BGCs. By assigning reads to known BGCs, putative BGCs were allocated in A7 that corresponded to various SMs, including naphthopyrone, pyranonigrin E, cyclopiazonic acids, etc. Based on gene homology analysis, we surmise that a region is involved in the biosynthesis of ustiloxin-like RiPPs, a less thoroughly studied SM in fungi. Our results provide genetic information for the investigation of marine Aspergillus sp., which may help to elucidate their chemical diversity and adaptive strategies.


Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5386
Author(s):  
Shean-Yeaw Ng ◽  
Chin-Soon Phan ◽  
Takahiro Ishii ◽  
Takashi Kamada ◽  
Toshiyuki Hamada ◽  
...  

Members of the marine soft coral genus Xenia are rich in a diversity of diterpenes. A total of 199 terpenes consisting of 14 sesquiterpenes, 180 diterpenes, and 5 steroids have been reported to date. Xenicane diterpenes were reported to be the most common chemical skeleton biosynthesized by members of this genus. Most of the literature reported the chemical diversity of Xenia collected from the coral reefs in the South China Sea and the coastal waters of Taiwan. Although there was a brief review on the terpenoids of Xenia in 2015, the present review is a comprehensive overview of the structural diversity of secondary metabolites isolated from soft coral genus Xenia and their potent biological activity as reported between 1977 to 2019.


Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 853 ◽  
Author(s):  
Mei-Mei Cheng ◽  
Xu-Li Tang ◽  
Yan-Ting Sun ◽  
Dong-Yang Song ◽  
Yu-Jing Cheng ◽  
...  

Marine sponges are well known as rich sources of biologically natural products. Growing evidence indicates that sponges harbor a wealth of microorganisms in their bodies, which are likely to be the true producers of bioactive secondary metabolites. In order to promote the study of natural product chemistry and explore the relationship between microorganisms and their sponge hosts, in this review, we give a comprehensive overview of the structures, sources, and activities of the 774 new marine natural products from sponge-derived microorganisms described over the last two decades from 1998 to 2017.


2021 ◽  
Author(s):  
Athina Gavriilidou ◽  
Satria A Kautsar ◽  
Nestor Zaburannyi ◽  
Daniel Krug ◽  
Rolf Mueller ◽  
...  

Bacterial secondary metabolites have been studied for decades for their usefulness as drugs, such as antibiotics. However, the identification of new structures has been decelerating, in part due to rediscovery of known compounds. Meanwhile, multi-resistant pathogens continue to emerge, urging the need for new antibiotics. It is unclear how much chemical diversity exists in Nature and whether discovery efforts should be focused on established antibiotic producers or rather on understudied taxa. Here, we surveyed around 170,000 bacterial genomes as well as several thousands of Metagenome Assembled Genomes (MAGs) for their diversity in Biosynthetic Gene Clusters (BGCs) known to encode the biosynthetic machinery for producing secondary metabolites. We used two distinct algorithms to provide a global overview of the biosynthetic diversity present in the sequenced part of the bacterial kingdom. Our results indicate that only 3% of genomic potential for natural products has been experimentally discovered. We connect the emergence of most biosynthetic diversity in evolutionary history close to the taxonomic rank of genus. Despite enormous differences in potential among taxa, we identify Streptomyces as by far the most biosynthetically diverse based on currently available data. Simultaneously, our analysis highlights multiple promising high-producing taxas that have thus far escaped investigation.


Planta Medica ◽  
2020 ◽  
Vol 86 (12) ◽  
pp. 805-821 ◽  
Author(s):  
Xiu-Qi Li ◽  
Kuo Xu ◽  
Xin-Min Liu ◽  
Peng Zhang

AbstractFungi are well known for their ability to synthesize secondary metabolites, which have proven to be a rich resource for exploring lead compounds with medicinal and/or agricultural importance. The genera Aspergillus, Penicillium, and Talaromyces are the most widely studied fungal groups, from which a plethora of bioactive metabolites have been characterized. However, relatively little attention has been paid to the genus Paecilomyces, which has been reported to possess great potential for its application as a biocontrol agent. Meanwhile, a wide structural array of metabolites with attractive bioactivities has been reported from this genus. This review attempts to provide a comprehensive overview of Paecilomyces species, with emphasis on the chemical diversity and relevant biological activities of these metabolic products. Herein, a total of 148 compounds and 80 references are cited in this review, which is expected to be beneficial for the development of medicines and agrochemicals in the near future.


2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Xin-Qing Zhao

Marine microorganisms are rich source for natural products which play important roles in pharmaceutical industry. Over the past decade, genome-based studies of marine microorganisms have unveiled the tremendous diversity of the producers of natural products and also contributed to the efficiency of harness the strain diversity and chemical diversity, as well as the genetic diversity of marine microorganisms for the rapid discovery and generation of new natural products. In the meantime, genomic information retrieved from marine symbiotic microorganisms can also be employed for the discovery of new medical molecules from yet-unculturable microorganisms. In this paper, the recent progress in the genomic research of marine microorganisms is reviewed; new tools of genome mining as well as the advance in the activation of orphan pathways and metagenomic studies are summarized. Genome-based research of marine microorganisms will maximize the biodiscovery process and solve the problems of supply and sustainability of drug molecules for medical treatments.


Antibiotics ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 86 ◽  
Author(s):  
Cláudia Vicente ◽  
Annabelle Thibessard ◽  
Jean-Noël Lorenzi ◽  
Mabrouka Benhadj ◽  
Laurence Hôtel ◽  
...  

Specialized metabolites are of great interest due to their possible industrial and clinical applications. The increasing number of antimicrobial resistant infectious agents is a major health threat and therefore, the discovery of chemical diversity and new antimicrobials is crucial. Extensive genomic data from Streptomyces spp. confirm their production potential and great importance. Genome sequencing of the same species strains indicates that specialized metabolite biosynthetic gene cluster (SMBGC) diversity is not exhausted, and instead, a pool of novel specialized metabolites still exists. Here, we analyze the genome sequence data from six phylogenetically close Streptomyces strains. The results reveal that the closer strains are phylogenetically, the number of shared gene clusters is higher. Eight specialized metabolites comprise the core metabolome, although some strains have only six core gene clusters. The number of conserved gene clusters common between the isolated strains and their closest phylogenetic counterparts varies from nine to 23 SMBGCs. However, the analysis of these phylogenetic relationships is not affected by the acquisition of gene clusters, probably by horizontal gene transfer events, as each strain also harbors strain-specific SMBGCs. Between one and 15 strain-specific gene clusters were identified, of which up to six gene clusters in a single strain are unknown and have no identifiable orthologs in other species, attesting to the existing SMBGC novelty at the strain level.


mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Heiko T. Kiesewalter ◽  
Carlos N. Lozano-Andrade ◽  
Mario Wibowo ◽  
Mikael L. Strube ◽  
Gergely Maróti ◽  
...  

ABSTRACT Bacillus subtilis produces a wide range of secondary metabolites providing diverse plant growth-promoting and biocontrol abilities. These secondary metabolites include nonribosomal peptides with strong antimicrobial properties, causing either cell lysis, pore formation in fungal membranes, inhibition of certain enzymes, or bacterial protein synthesis. However, the natural products of B. subtilis are mostly studied either in laboratory strains or in individual isolates, and therefore, a comparative overview of secondary metabolites from various environmental B. subtilis strains is missing. In this study, we isolated 23 B. subtilis strains from 11 sampling sites, compared the fungal inhibition profiles of wild types and their nonribosomal peptide mutants, followed the production of targeted lipopeptides, and determined the complete genomes of 13 soil isolates. We discovered that nonribosomal peptide production varied among B. subtilis strains coisolated from the same soil samples. In vitro antagonism assays revealed that biocontrol properties depend on the targeted plant pathogenic fungus and the tested B. subtilis isolate. While plipastatin alone is sufficient to inhibit Fusarium spp., a combination of plipastatin and surfactin is required to hinder growth of Botrytis cinerea. Detailed genomic analysis revealed that altered nonribosomal peptide production profiles in specific isolates are due to missing core genes, nonsense mutation, or potentially altered gene regulation. Our study combines microbiological antagonism assays with chemical nonribosomal peptide detection and biosynthetic gene cluster predictions in diverse B. subtilis soil isolates to provide a broader overview of the secondary metabolite chemodiversity of B. subtilis. IMPORTANCE Secondary or specialized metabolites with antimicrobial activities define the biocontrol properties of microorganisms. Members of the Bacillus genus produce a plethora of secondary metabolites, of which nonribosomally produced lipopeptides in particular display strong antifungal activity. To facilitate the prediction of the biocontrol potential of new Bacillus subtilis isolates, we have explored the in vitro antifungal inhibitory profiles of recent B. subtilis isolates, combined with analytical natural product chemistry, mutational analysis, and detailed genome analysis of biosynthetic gene clusters. Such a comparative analysis helped to explain why selected B. subtilis isolates lack the production of certain secondary metabolites.


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