scholarly journals Secondary Metabolite Production Potential of Mangrove-Derived Streptomyces olivaceus

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 332
Author(s):  
Dini Hu ◽  
Simon Ming-Yuen Lee ◽  
Kai Li ◽  
Kai Meng Mok
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Fermentation Broth ◽  
Genome Mining ◽  
Extreme Environments ◽  
Gene Clusters ◽  
Secondary Metabolite Production ◽  
Production Potential ◽  
Metabolite Production ◽  
Streptomyces Olivaceus

Mangroves are intertidal extreme environments with rich microbial communities. Actinobacteria are well known for producing antibiotics. The search for biosynthetic potential of Actinobacteria from mangrove environments could provide more possibilities for useful secondary metabolites. In this study, whole genome sequencing and MS/MS analysis were used to explore the secondary metabolite production potential of one actinobacterial strain of Streptomyces olivaceus sp., isolated from a mangrove in Macau, China. The results showed that a total of 105 gene clusters were found in the genome of S. olivaceus sp., and 53 known secondary metabolites, including bioactive compounds, peptides, and other products, were predicted by genome mining. There were 28 secondary metabolites classified as antibiotics, which were not previously known from S. olivaceus. ISP medium 2 was then used to ferment the S. olivaceus sp. to determine which predicted secondary metabolite could be truly produced. The chemical analysis revealed that ectoine, melanin, and the antibiotic of validamycin A could be observed in the fermentation broth. This was the first observation that these three compounds can be produced by a strain of S. olivaceus. Therefore, it can be concluded that Actinobacteria isolated from the mangrove environment have unknown potential to produce bioactive secondary metabolites.

scholarly journals Boosting Secondary Metabolite Production and Discovery through the Engineering of Novel Microbial Biosensors

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ulysses Amancio de Frias ◽  
Greicy Kelly Bonifacio Pereira ◽  
María-Eugenia Guazzaroni ◽  
Rafael Silva-Rocha
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Gene Clusters ◽  
Secondary Metabolite Production ◽  
Special Focus ◽  
Biosynthetic Gene ◽  
Expression Systems ◽  
Biosynthetic Gene Clusters ◽  
Metabolite Production ◽  
Synthetic Promoters

Bacteria are a source of a large number of secondary metabolites with several biomedical and biotechnological applications. In recent years, there has been tremendous progress in the development of novel synthetic biology approaches both to increase the production rate of secondary metabolites of interest in native producers and to mine and reconstruct novel biosynthetic gene clusters in heterologous hosts. Here, we present the recent advances toward the engineering of novel microbial biosensors to detect the synthesis of secondary metabolites in bacteria and in the development of synthetic promoters and expression systems aiming at the construction of microbial cell factories for the production of these compounds. We place special focus on the potential of Gram-negative bacteria as a source of biosynthetic gene clusters and hosts for pathway assembly, on the construction and characterization of novel promoters for native hosts, and on the use of computer-aided design of novel pathways and expression systems for secondary metabolite production. Finally, we discuss some of the potentials and limitations of the approaches that are currently being developed and we highlight new directions that could be addressed in the field.

scholarly journals Comparative Genomics Determines Strain-Dependent Secondary Metabolite Production in Streptomyces venezuelae Strains

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 864
Author(s):  
Woori Kim ◽  
Namil Lee ◽  
Soonkyu Hwang ◽  
Yongjae Lee ◽  
Jihun Kim ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Gene Clusters ◽  
Secondary Metabolite Production ◽  
Biosynthetic Gene ◽  
Genome Sequences ◽  
Biosynthetic Gene Clusters ◽  
Streptomyces Venezuelae ◽  
Metabolite Production ◽  
Non Coding Rna

Streptomyces venezuelae is well known to produce various secondary metabolites, including chloramphenicol, jadomycin, and pikromycin. Although many strains have been classified as S. venezuelae species, only a limited number of strains have been explored extensively for their genomic contents. Moreover, genomic differences and diversity in secondary metabolite production between the strains have never been compared. Here, we report complete genome sequences of three S. venezuelae strains (ATCC 10712, ATCC 10595, and ATCC 21113) harboring chloramphenicol and jadomycin biosynthetic gene clusters (BGC). With these high-quality genome sequences, we revealed that the three strains share more than 85% of total genes and most of the secondary metabolite biosynthetic gene clusters (smBGC). Despite such conservation, the strains produced different amounts of chloramphenicol and jadomycin, indicating differential regulation of secondary metabolite production at the strain level. Interestingly, antagonistic production of chloramphenicol and jadomycin was observed in these strains. Through comparison of the chloramphenicol and jadomycin BGCs among the three strains, we found sequence variations in many genes, the non-coding RNA coding regions, and binding sites of regulators, which affect the production of the secondary metabolites. We anticipate that these genome sequences of closely related strains would serve as useful resources for understanding the complex secondary metabolism and for designing an optimal production process using Streptomyces strains.

scholarly journals Differential regulation and production of secondary metabolites among isolates of the fungal wheat pathogen Zymoseptoria tritici

2021 ◽  
Author(s):  
M. Amine Hassani ◽  
Ernest Oppong-Danquah ◽  
Alice Feurty ◽  
Deniz Tasdemir ◽  
Eva H Stukenbrock
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Expression Profiles ◽  
Pathogenic Fungus ◽  
Gene Clusters ◽  
Secondary Metabolite Production ◽  
Zymoseptoria Tritici ◽  
Host Colonization ◽  
Metabolite Production

The genome of the wheat pathogenic fungus, Zymoseptoria tritici, represents extensive presence-absence variation in gene content. Here, we addressed variation in biosynthetic gene clusters (BGCs) content and biochemical profiles among three isolates. We analysed secondary metabolite properties based on genome, transcriptome and metabolome data. The isolates represent highly distinct genome architecture, but harbor similar repertoire of BGCs. Expression profiles for most BGCs show comparable patterns of regulation among the isolates, suggesting a conserved 'biochemical infection program'. For all three isolates, we observed a strong up-regulation of an abscisic acid (ABA) gene cluster during biotrophic host colonization, indicating that Z. tritici potentially interfere with host defenses by the biosynthesis of this phytohormone. Further, during in vitro growth the isolates show similar metabolomes congruent with the predicted BGC content. We assessed if secondary metabolite production is regulated by histone methylation using a mutant impaired in formation of facultative heterochromatin (H3K27me3). In contrast to other ascomycete fungi, chromatin modifications play a less prominent role in regulation of secondary metabolites. In summary, we show that Z. tritici has a conserved program of secondary metabolite production contrasting the immense variation in effector expression, some of these metabolites might play a key role during host colonization.

scholarly journals Triaging of Culture Conditions for the Enhanced Discovery of Secondary Metabolites from Different Bacteria

2020 ◽  
Author(s):  
Jenny Schwarz ◽  
Stephan Lütz
Keyword(s):  
Secondary Metabolite ◽  
Genome Mining ◽  
Gene Clusters ◽  
Culture Conditions ◽  
Secondary Metabolite Production ◽  
Bacterial Strains ◽  
Metabolite Production ◽  
Desferrioxamine B ◽  
Prior Literature ◽  
Literature Coverage

Over the past decade, the One Strain Many Compounds (OSMAC) approach has been established for silent gene cluster activation and elicitation of secondary metabolite production, but so far the full secondary metabolome of a biosynthetically promising bacterium has not been elucidated yet. Here, we investigate the ability of seven categories of OSMAC conditions to elicit new mass features from bacterial strains with little literature coverage but high biosynthetic potential. The strains B. amyloliquefaciens DSM7, C. coralloides DSM2259, P. fallax HKI727, R. jostii DSM44719 and S. griseochromogenes DSM40499 were selected after genome mining with antiSMASH. After cultivation under OSMAC conditions, the generated extracts were subjected to LC/MS and MZmine analysis to determine new mass features, expressed gene clusters and evaluate the tested culture conditions. 4 predicted compounds, bacillibactin, desferrioxamine B, myxochelin A and surfactin, were identified and up to 147 new mass features were detected in the generated extracts, which greatly surpasses the number of predicted gene clusters. Among the new mass features are bioactive compounds which were so far unreported for the strains such as cyclo-(Tyr-Pro) from DSM7 and nocardamin from DSM2259. Furthermore, the tested culture conditions were evaluated regarding their suitability for the generation of new mass features from the selected strains and promising new starting points for further screenings are postulated. Especially culture conditions with little prior literature coverage are responsible for the activation of secondary metabolite production.

scholarly journals Urgensi dan Mekanisme Biosintesis Metabolit Sekunder Mikroba Laut

2012 ◽  
Vol 10 (2) ◽  
pp. 120 ◽  
Author(s):  
Risa Nofiani
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Metabolic Pathways ◽  
Abiotic Factors ◽  
Biologically Active ◽  
Secondary Metabolite Production ◽  
Marine Microorganism ◽  
Metabolite Production ◽  
Biotic And Abiotic Factors ◽  
Living Materials

Marine microorganism is one of biologically active potential resources of secondary metabolites. Its potency areso promising that the knowledge of how its secondary metabolite occured need to be studied and collected. Thoseknowledges will enable further study is improving secondary metabolite production in the laboratory. In nature,secondary metabolites synthesis occur when there are effect of both biotic and abiotic factors such as sea waterand microbe symbiosis with other living materials. When this is explained in metabolic pathways, secondarymetabolite synthesis affected by available nutrient and regulated by autoinducer molecules through quorum sensingmechanism

scholarly journals Phylogenetic Distribution of Secondary Metabolites in the Bacillus subtilis Species Complex

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Kat Steinke ◽  
Omkar S. Mohite ◽  
Tilmann Weber ◽  
Ákos T. Kovács
Keyword(s):  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Species Complex ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Content Type ◽  
Frameshift Mutations ◽  
Metabolite Production

ABSTRACT Microbes produce a plethora of secondary (or specialized) metabolites that, although not essential for primary metabolism, benefit them to survive in the environment, communicate, and influence cell differentiation. Biosynthetic gene clusters (BGCs), responsible for the production of these secondary metabolites, are readily identifiable on bacterial genome sequences. Understanding the phylogeny and distribution of BGCs helps us to predict the natural product synthesis ability of new isolates. Here, we examined 310 genomes from the Bacillus subtilis group, determined the inter- and intraspecies patterns of absence/presence for all BGCs, and assigned them to defined gene cluster families (GCFs). This allowed us to establish patterns in the distribution of both known and unknown products. Further, we analyzed variations in the BGC structures of particular families encoding natural products, such as plipastatin, fengycin, iturin, mycosubtilin, and bacillomycin. Our detailed analysis revealed multiple GCFs that are species or clade specific and a few others that are scattered within or between species, which will guide exploration of the chemodiversity within the B. subtilis group. Surprisingly, we discovered that partial deletion of BGCs and frameshift mutations in selected biosynthetic genes are conserved within phylogenetically related isolates, although isolated from around the globe. Our results highlight the importance of detailed genomic analysis of BGCs and the remarkable phylogenetically conserved erosion of secondary metabolite biosynthetic potential in the B. subtilis group. IMPORTANCE Members of the B. subtilis species complex are commonly recognized producers of secondary metabolites, among those, the production of antifungals, which makes them promising biocontrol strains. While there are studies examining the distribution of well-known secondary metabolites in Bacilli, intraspecies clade-specific distribution has not been systematically reported for the B. subtilis group. Here, we report the complete biosynthetic potential within the B. subtilis group to explore the distribution of the biosynthetic gene clusters and to reveal an exhaustive phylogenetic conservation of secondary metabolite production within Bacillus that supports the chemodiversity within this species complex. We identify that certain gene clusters acquired deletions of genes and particular frameshift mutations, rendering them inactive for secondary metabolite biosynthesis, a conserved genetic trait within phylogenetically conserved clades of certain species. The overview guides the assignment of the secondary metabolite production potential of newly isolated Bacillus strains based on genome sequence and phylogenetic relatedness.

scholarly journals Deletion of the Histone Deacetylase HdaA in Endophytic Fungus Penicillium chrysogenum Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster Expression

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3657 ◽  
Author(s):  
Zhuang Ding ◽  
Haibo Zhou ◽  
Xiao Wang ◽  
Huiming Huang ◽  
Haotian Wang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Secondary Metabolite ◽  
Endophytic Fungus ◽  
Penicillium Chrysogenum ◽  
Gene Clusters ◽  
Transcriptional Analysis ◽  
Secondary Metabolite Production ◽  
Metabolite Production ◽  
Epigenetic Regulator ◽  
Relevant Gene

Epigenetic regulation plays a critical role in controlling fungal secondary metabolism. Here, we report the pleiotropic effects of the epigenetic regulator HdaA (histone deacetylase) on secondary metabolite production and the associated biosynthetic gene clusters (BGCs) expression in the plant endophytic fungus Penicillium chrysogenum Fes1701. Deletion of the hdaA gene in strain Fes1701 induced a significant change of the secondary metabolite profile with the emergence of the bioactive indole alkaloid meleagrin. Simultaneously, more meleagrin/roquefortine-related compounds and less chrysogine were synthesized in the ΔhdaA strain. Transcriptional analysis of relevant gene clusters in ΔhdaA and wild strains indicated that disruption of hdaA had different effects on the expression levels of two BGCs: the meleagrin/roquefortine BGC was upregulated, while the chrysogine BGC was downregulated. Interestingly, transcriptional analysis demonstrated that different functional genes in the same BGC had different responses to the disruption of hdaA. Thereinto, the roqO gene, which encodes a key catalyzing enzyme in meleagrin biosynthesis, showed the highest upregulation in the ΔhdaA strain (84.8-fold). To our knowledge, this is the first report of the upregulation of HdaA inactivation on meleagrin/roquefortine alkaloid production in the endophytic fungus P. chrysogenum. Our results suggest that genetic manipulation based on the epigenetic regulator HdaA is an important strategy for regulating the productions of secondary metabolites and expanding bioactive natural product resources in endophytic fungi.

scholarly journals Unlocking Pharmacological and Therapeutic Potential of Hyacinth Bean (Lablab purpureus L.): Role of OMICS Based Biology, Biotic and Abiotic Elicitors

2021 ◽  
Author(s):  
Krishna Kumar Rai ◽  
Nagendra Rai ◽  
Shashi Pandey-Rai
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Secondary Metabolite Production ◽  
Metabolite Production ◽  
Genetic Potential ◽  
Abiotic Elicitors ◽  
Hyacinth Bean ◽  
Underutilised Crops

Hyacinth bean also known as Indian bean is multipurpose legume crops consumed both as food by humans and as forage by animals. Being a rich source of protein, it also produces distinct secondary metabolites such as flavonoids, phenols and tyrosinase which not only help strengthened plant’s own innate immunity against abiotic/biotrophic attackers but also play important therapeutic role in the treatment of various chronic diseases. However, despite its immense therapeutic and nutritional attributes in strengthening food, nutrition and therapeutic security in many developing countries, it is still considered as an “orphan crop” for unravelling its genetic potential and underlying molecular mechanisms for enhancing secondary metabolite production. Several lines of literatures have well documented the use of OMICS based techniques and biotic and abiotic elicitors for stimulating secondary metabolite production particularly in model as well as in few economically important crops. However, only limited reports have described their application for stimulating secondary metabolite production in underutilised crops. Therefore, the present chapter will decipher different dimensions of multi-omics tools and their integration with other conventional techniques (biotic and abiotic elicitors) for unlocking hidden genetic potential of hyacinth bean for elevating the production of secondary metabolites having pharmaceutical and therapeutic application. Additionally, the study will also provide valuable insights about how these advance OMICS tools can be successfully exploited for accelerating functional genomics and breeding research for unravelling their hidden pharmaceutical and therapeutic potential thereby ensuring food and therapeutic security for the betterment of mankind.

scholarly journals Genome mining and UHPLC-MS/MS illuminate the specificity of secondary metabolite synthetic gene clusters in Bacillus subtilis NCD-2

2020 ◽  
Author(s):  
Zhenhe Su ◽  
Xiuye Chen ◽  
Xiaomeng Liu ◽  
Qinggang Guo ◽  
Shezeng Li ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Biological Activities ◽  
Genome Mining ◽  
Gene Clusters ◽  
Synthetic Gene ◽  
Integrative Approach ◽  
Amino Acid Sequence Similarity ◽  
Genetic Characteristics

Abstract Background Bacillus subtilisstrain NCD-2 is anexcellent biocontrol agent against plant soil-borne diseases and shows broad-spectrum antifungal activities. This study aimed to explore all the secondary metabolite synthetic gene clusters and related bioactive compounds in NCD-2. An integrative approach, which coupled genome mining with structural identification technologies using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-MS/MS), was conducted to interpret the chemical origins of the significant biological activities in NCD-2. Results Genome mining revealed that NCD-2 contained nine gene clustershaving predicted functionsinvolving secondary metabolites with bioactive abilities. They encoded six known products-fengycin, surfactin, bacillaene, subtilosin, bacillibactin, and bacilysin-as well as three unknown products.Interestingly, the synthetic gene clusters for surfactin and fengycin showed 83% and 92% amino acid sequence similarity levels with the corresponding productsin Bacillus velezensisstrain FZB42. A further comparison of gene clusters encoding fengycin and surfactinrevealed that strain NCD-2 had lost thefenC and fenDgenes in the fengycinbiosynthetic operon, and that the surfactin synthetic enzyme-related gene srfAB was divided into two parts.Abioinformatics analysis showed that fenEAmay function as fenCD in synthesizing fengycinand that the structure of thisfengycin synthetic gene clusteris likely unique to NCD-2.Five kinds of fengycin,with 26 homologs, and surfactin,with 4 homologs,were detectedfrom strain NCD-2, which indicated the non-typical and unique nature of this fengycin biosynthetic gene cluster.To the best of our knowledge, this is the first report of a non-typical gene cluster related to fengycin synthesis. Conclusions The data provide the genetic characteristics of secondary metabolite synthetic gene clusters for fengycinand surfactin in B. subtilis NCD-2, including the unique synthetic mechanism for fengycin, and suggest that bioactive secondary metabolites explain the biological activities of NCD-2.

scholarly journals Cleaning the Cellular Factory–Deletion of McrA in Aspergillus oryzae NSAR1 and the Generation of a Novel Kojic Acid Deficient Strain for Cleaner Heterologous Production of Secondary Metabolites

2021 ◽  
Vol 2 ◽  
Author(s):  
Trong T. Dao ◽  
Kate M. J. de Mattos-Shipley ◽  
Ian M. Prosser ◽  
Katherine Williams ◽  
Marija K. Zacharova ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Natural Product ◽  
Secondary Metabolite ◽  
Aspergillus Oryzae ◽  
Kojic Acid ◽  
Negative Regulator ◽  
Secondary Metabolite Production ◽  
Phenotypic Change ◽  
Metabolite Production ◽  
Host Strains

The use of filamentous fungi as cellular factories, where natural product pathways can be refactored and expressed in a host strain, continues to aid the field of natural product discovery. Much work has been done to develop host strains which are genetically tractable, and for which there are multiple selectable markers and controllable expression systems. To fully exploit these strains, it is beneficial to understand their natural metabolic capabilities, as such knowledge can rule out host metabolites from analysis of transgenic lines and highlight any potential interplay between endogenous and exogenous pathways. Additionally, once identified, the deletion of secondary metabolite pathways from host strains can simplify the detection and purification of heterologous compounds. To this end, secondary metabolite production in Aspergillus oryzae strain NSAR1 has been investigated via the deletion of the newly discovered negative regulator of secondary metabolism, mcrA (multicluster regulator A). In all ascomycetes previously studied mcrA deletion led to an increase in secondary metabolite production. Surprisingly, the only detectable phenotypic change in NSAR1 was a doubling in the yields of kojic acid, with no novel secondary metabolites produced. This supports the previous claim that secondary metabolite production has been repressed in A. oryzae and demonstrates that such repression is not McrA-mediated. Strain NSAR1 was then modified by employing CRISPR-Cas9 technology to disrupt the production of kojic acid, generating the novel strain NSARΔK, which combines the various beneficial traits of NSAR1 with a uniquely clean secondary metabolite background.

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