scholarly journals Identification of microRNAs from Medicinal Plant Murraya koenigii by High-Throughput Sequencing and Their Functional Implications in Secondary Metabolite Biosynthesis

Plants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 46
Author(s):  
Claudia Gutiérrez-García ◽  
Shiek S. S. J. Ahmed ◽  
Sathishkumar Ramalingam ◽  
Dhivya Selvaraj ◽  
Aashish Srivastava ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Medicinal Plant ◽  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
High Throughput ◽  
Noncoding Rna ◽  
High Throughput Sequencing ◽  
Mirna Profile ◽  
Murraya Koenigii ◽  
Secondary Metabolite Biosynthesis

MicroRNAs (miRNAs) are small noncoding RNA molecules that play crucial post-transcriptional regulatory roles in plants, including development and stress-response signaling. However, information about their involvement in secondary metabolism is still limited. Murraya koenigii is a popular medicinal plant, better known as curry leaves, that possesses pharmaceutically active secondary metabolites. The present study utilized high-throughput sequencing technology to investigate the miRNA profile of M. koenigii and their association with secondary metabolite biosynthesis. A total of 343,505 unique reads with lengths ranging from 16 to 40 nt were obtained from the sequencing data, among which 142 miRNAs were identified as conserved and 7 as novel miRNAs. Moreover, 6078 corresponding potential target genes of M. koenigii miRNAs were recognized in this study. Interestingly, several conserved and novel miRNAs of M. koenigii were found to target key enzymes of the terpenoid backbone and the flavonoid biosynthesis pathways. Furthermore, to validate the sequencing results, the relative expression of eight randomly selected miRNAs was determined by qPCR. To the best of our knowledge, this is the first report of the M. koenigii miRNA profile that may provide useful information for further elucidation of the involvement of miRNAs in secondary metabolism. These findings might be crucial in the future to generate artificial-miRNA-based, genetically engineered M. koenigii plants for the overproduction of medicinally highly valuable secondary metabolites.

Regio- and stereoselective intermolecular phenol coupling enzymes in secondary metabolite biosynthesis

2021 ◽  
Author(s):  
Wolfgang Hüttel ◽  
Michael Müller
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Metabolic Pathways ◽  
Cyp Enzymes ◽  
Secondary Metabolite Biosynthesis

Phenol coupling enzymes, especially laccases and CYP-enzymes create an enormous diversity of biarylic secondary metabolites in fungi, plants, and bacteria. The enzymes and the elucidation of the corresponding metabolic pathways are presented.

scholarly journals Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi

mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Jens Christian Nielsen ◽  
Sylvain Prigent ◽  
Sietske Grijseels ◽  
Mhairi Workman ◽  
Boyang Ji ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
Filamentous Fungi ◽  
Metabolic Regulation ◽  
Fungal Species ◽  
Efficient Production ◽  
Fungal Cell ◽  
Fungal Metabolism ◽  
Cell Factories

ABSTRACTFilamentous fungi possess great potential as sources of medicinal bioactive compounds, such as antibiotics, but efficient production is hampered by a limited understanding of how their metabolism is regulated. We investigated the metabolism of six secondary metabolite-producing fungi of thePenicilliumgenus during nutrient depletion in the stationary phase of batch fermentations and assessed conserved metabolic responses across species using genome-wide transcriptional profiling. A coexpression analysis revealed that expression of biosynthetic genes correlates with expression of genes associated with pathways responsible for the generation of precursor metabolites for secondary metabolism. Our results highlight the main metabolic routes for the supply of precursors for secondary metabolism and suggest that the regulation of fungal metabolism is tailored to meet the demands for secondary metabolite production. These findings can aid in identifying fungal species that are optimized for the production of specific secondary metabolites and in designing metabolic engineering strategies to develop high-yielding fungal cell factories for production of secondary metabolites.IMPORTANCESecondary metabolites are a major source of pharmaceuticals, especially antibiotics. However, the development of efficient processes of production of secondary metabolites has proved troublesome due to a limited understanding of the metabolic regulations governing secondary metabolism. By analyzing the conservation in gene expression across secondary metabolite-producing fungal species, we identified a metabolic signature that links primary and secondary metabolism and that demonstrates that fungal metabolism is tailored for the efficient production of secondary metabolites. The insight that we provide can be used to develop high-yielding fungal cell factories that are optimized for the production of specific secondary metabolites of pharmaceutical interest.

scholarly journals Variation Among Biosynthetic Gene Clusters, Secondary Metabolite Profiles, and Cards of Virulence Across Aspergillus Species

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 481-497 ◽  
Author(s):  
Jacob L. Steenwyk ◽  
Matthew E. Mead ◽  
Sonja L. Knowles ◽  
Huzefa A. Raja ◽  
Christopher D. Roberts ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
Immune Cell ◽  
Sequence Divergence ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Host Immune System ◽  
Biosynthetic Gene ◽  
Genetic Determinants

Aspergillus fumigatus is a major human pathogen. In contrast, Aspergillus fischeri and the recently described Aspergillus oerlinghausenensis, the two species most closely related to A. fumigatus, are not known to be pathogenic. Some of the genetic determinants of virulence (or “cards of virulence”) that A. fumigatus possesses are secondary metabolites that impair the host immune system, protect from host immune cell attacks, or acquire key nutrients. To examine whether secondary metabolism-associated cards of virulence vary between these species, we conducted extensive genomic and secondary metabolite profiling analyses of multiple A. fumigatus, one A. oerlinghausenensis, and multiple A. fischeri strains. We identified two cards of virulence (gliotoxin and fumitremorgin) shared by all three species and three cards of virulence (trypacidin, pseurotin, and fumagillin) that are variable. For example, we found that all species and strains examined biosynthesized gliotoxin, which is known to contribute to virulence, consistent with the conservation of the gliotoxin biosynthetic gene cluster (BGC) across genomes. For other secondary metabolites, such as fumitremorgin, a modulator of host biology, we found that all species produced the metabolite but that there was strain heterogeneity in its production within species. Finally, species differed in their biosynthesis of fumagillin and pseurotin, both contributors to host tissue damage during invasive aspergillosis. A. fumigatus biosynthesized fumagillin and pseurotin, while A. oerlinghausenensis biosynthesized fumagillin and A. fischeri biosynthesized neither. These biochemical differences were reflected in sequence divergence of the intertwined fumagillin/pseurotin BGCs across genomes. These results delineate the similarities and differences in secondary metabolism-associated cards of virulence between a major fungal pathogen and its nonpathogenic closest relatives, shedding light onto the genetic and phenotypic changes associated with the evolution of fungal pathogenicity.

scholarly journals Lysobacter enzymogenes Uses Two Distinct Cell-Cell Signaling Systems for Differential Regulation of Secondary-Metabolite Biosynthesis and Colony Morphology

2013 ◽  
Vol 79 (21) ◽  
pp. 6604-6616 ◽  
Author(s):  
Guoliang Qian ◽  
Yulan Wang ◽  
Yiru Liu ◽  
Feifei Xu ◽  
Ya-Wen He ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Cell Signaling ◽  
Secondary Metabolite ◽  
Colony Morphology ◽  
Content Type ◽  
Signaling Systems ◽  
Lysobacter Enzymogenes ◽  
Bioactive Secondary Metabolites ◽  
Secondary Metabolite Biosynthesis ◽  
First Time

ABSTRACTLysobacter enzymogenesis a ubiquitous environmental bacterium that is emerging as a potentially novel biological control agent and a new source of bioactive secondary metabolites, such as the heat-stable antifungal factor (HSAF) and photoprotective polyene pigments. Thus far, the regulatory mechanism(s) for biosynthesis of these bioactive secondary metabolites remains largely unknown inL. enzymogenes. In the present study, the diffusible signal factor (DSF) and diffusible factor (DF)-mediated cell-cell signaling systems were identified for the first time fromL. enzymogenes. The results show that both Rpf/DSF and DF signaling systems played critical roles in modulating HSAF biosynthesis inL. enzymogenes. Rpf/DSF signaling and DF signaling played negative and positive effects in polyene pigment production, respectively, with DF playing a more important role in regulating this phenotype. Interestingly, only Rpf/DSF, but not the DF signaling system, regulated colony morphology ofL. enzymgenes. Both Rpf/DSF and DF signaling systems were involved in the modulation of expression of genes with diverse functions inL. enzymogenes, and their own regulons exhibited only a few loci that were regulated by both systems. These findings unveil for the first time new roles of the Rpf/DSF and DF signaling systems in secondary metabolite biosynthesis ofL. enzymogenes.

scholarly journals WblA, a global regulator of antibiotic biosynthesis in Streptomyces

2021 ◽  
Author(s):  
Hee-Ju Nah ◽  
Jihee Park ◽  
Sisun Choi ◽  
Eung-Soo Kim
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Anticancer Drugs ◽  
Regulatory Networks ◽  
The Other ◽  
Antibiotic Biosynthesis ◽  
Global Regulator ◽  
Streptomyces Species ◽  
The Past ◽  
Secondary Metabolite Biosynthesis

Abstract Streptomyces species are soil-dwelling bacteria that produce vast numbers of pharmaceutically valuable secondary metabolites, such as antibiotics, immunosuppressants, antiviral, and anticancer drugs. On the other hand, the biosynthesis of most secondary metabolites remains very low due to tightly controlled regulatory networks. Both global and pathway-specific regulators are involved in the regulation of a specific secondary metabolite biosynthesis in various Streptomyces species. Over the past few decades, many of these regulators have been identified and new ones are still being discovered. Among them, a global regulator of secondary metabolite biosynthesis named WblA was identified in several Streptomyces species. The identification and understanding of the WblAs have greatly contributed to increasing the productivity of several Streptomyces secondary metabolites. This review summarizes the characteristics and applications on WblAs reported to date, which were found in various Streptomyces species and other actinobacteria.

Application of High-Throughput Sequencing in Medicinal Plant Transcriptome Studies

2012 ◽  
Vol 73 (8) ◽  
pp. 487-498 ◽  
Author(s):  
Da-Cheng Hao ◽  
Shi-Lin Chen ◽  
Pei-Gen Xiao ◽  
Ming Liu
Keyword(s):  
Medicinal Plant ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Plant Transcriptome

scholarly journals Analysis of Endophyte Diversity of Rheum palmatum from Different Production Areas in Gansu Province of China and the Association with Secondary Metabolite

2021 ◽  
Vol 9 (5) ◽  
pp. 978
Author(s):  
Dawei Chen ◽  
Lingyun Jia ◽  
Qinzheng Hou ◽  
Xiang Zhao ◽  
Kun Sun
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Endophytic Fungi ◽  
High Throughput Sequencing ◽  
Gansu Province ◽  
Operational Taxonomic Units ◽  
Rheum Palmatum ◽  
Microbe Interactions ◽  
Production Area ◽  
Production Areas

Investigations of the differences in the metabolites of medicinal plants have typically focused on the effects of external environmental factors. However, little is known about the relationship between endophytes diversity and host metabolites. We used high-throughput sequencing methods to compare the endophyte diversity of Rheum palmatum from eight different production areas in Gansu Province of China and to analyze the association between those areas and five secondary metabolites (aloe-emodin, rhein, emodin, chrysophanol, and physcion). The results show that the diversity and OTUs (Operational taxonomic units) abundance of endophytic fungi and bacteria of R. palmatum differed according to production area. Spearman analysis showed that the five secondary metabolites of R. palmatum were positively correlated with the diversity and abundance of endophytic fungi. Comparing both space and environmental differences to determine influences on community structure, VPA analysis revealed that geographic factors explained more difference in community composition of fungal and bacterial endophytes than climate factors. PICRUSt and FUNGuild predictive analysis indicated that metabolites were the primary components of endophytic bacteria in all samples, while the function of endophytic fungi was composed of dominant trophic modes (saprotroph and pathotroph), and relative abundances were different. Our results help elucidate the correlation of plant–microbe interactions and offer pivotal information to reveal the role of endophytes in the production of R. palmatum and its important secondary metabolite.

scholarly journals Melatonin alters the secondary metabolite profile of grape berry skin by promoting VvMYB14-mediated ethylene biosynthesis

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Wanyun Ma ◽  
Lili Xu ◽  
Shiwei Gao ◽  
Xingning Lyu ◽  
Xiaolei Cao ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Metabolite Profile ◽  
Ethylene Biosynthesis ◽  
Grape Berry ◽  
Rna Seq ◽  
Melatonin Treatment ◽  
Berry Skin ◽  
Secondary Metabolite Biosynthesis ◽  
Widely Targeted Metabolomics

AbstractThe interplay between melatonin and ethylene in the regulation of fruit metabolism and the underlying molecular mechanism of this interplay remain largely unclear. Here, widely targeted metabolomics analysis revealed a total of 464 metabolites present in berry skin. Among them, 27 significantly differentially accumulated metabolites (DAMs) were produced in response to melatonin treatment in the presence or absence of 1-MCP. Most of the DAMs were secondary metabolites, including flavonoids, phenolic acids, stilbenes, and flavonols. Additionally, the accumulation of 25 DAMs was regulated by melatonin via ethylene. RNA-seq analysis indicated that melatonin primarily regulated the pathways of plant hormone signal transduction and secondary metabolite biosynthesis via ethylene. Gene-metabolite association analysis showed that melatonin regulated the expression of the VvSTS1, VvF3H, VvLAR2, and VvDFR genes, suggesting that these genes may play key roles in regulating secondary metabolites in the skin; additionally, VvMYB14 and VvACS1 were suggested to be involved in the regulation of secondary metabolites. Further experiments revealed that melatonin induced the expression of VvMYB14 and that VvMYB14 increased ethylene production by transcriptionally activating VvACS1, thereby affecting the accumulation of secondary metabolites. Collectively, melatonin promotes ethylene biosynthesis and alters secondary metabolite accumulation through the regulation of VvACS1 by VvMYB14.

From molecular genetics and secondary metabolism to molecular metabolites and secondary genetics

1995 ◽  
Vol 73 (S1) ◽  
pp. 917-924 ◽  
Author(s):  
J. W. Bennett
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
Fatty Acid Biosynthesis ◽  
Morphological Characters ◽  
Model Systems ◽  
Chain Elongation ◽  
Research Approach ◽  
Active Growth ◽  
Hybrid Molecules

Secondary metabolites constitute a huge array of low molecular weight natural products that cannot be easily defined. Largely produced by bacteria, fungi, and green plants, they tend to be synthesized after active growth has ceased, in families of similar compounds, often at the same time as species-specific morphological characters become apparent. Although, in many cases, the function that the secondary metabolite performs in the producing organism is unknown, the bioactivity of these compounds has been exploited since prehistoric times as drugs, poisons, food flavoring agents, and so forth. In fungi, the polyketide family is the largest known group of secondary metabolite compounds. Polyketides are synthesized from acetate by a mechanism analogous to fatty acid biosynthesis but involving changes in oxidation level and stereochemistry during the chain-elongation process. The fungal polyketide biosynthetic pathways for aflatoxin and patulin have emerged as model systems. The use of blocked mutants has been an essential part of the research approach for both pathways. Molecular methods of studying fungal secondary metabolites were first used with penicillin and cephalosporin, both of which are amino acid derived. Most of the basic molecular work on polyketides was done with streptomycete-derived compounds; however, enough fungal data are now available to compare fungal and streptomycete polyketide synthases, as well as to map the genes involved in a number of polyketide pathways from both groups. The traditional dogma, derived from classical genetics, that genes for fungal pathways are unlinked, has been overturned. In addition, cloning of structural genes facilitates the formation of hybrid molecules, and we are on the brink of understanding certain regulatory functions. Key words: fungal metabolism, secondary metabolism, polyketide, β-lactam, product discovery.

scholarly journals Transcriptome analysis of North American sweet birch (Betula lenta) revealed a higher expression of genes involved in the biosynthesis of secondary metabolites than European silver birch (B. pendula)

2021 ◽  
Vol 134 (6) ◽  
pp. 1253-1264
Author(s):  
Kiran Singewar ◽  
Birgit Kersten ◽  
Christian R. Moschner ◽  
Eberhard Hartung ◽  
Matthias Fladung
Keyword(s):  
Native Americans ◽  
Secondary Metabolites ◽  
Candidate Genes ◽  
Secondary Metabolite ◽  
Transcriptome Analysis ◽  
North American ◽  
Regulatory Elements ◽  
Silver Birch ◽  
Secondary Metabolite Biosynthesis ◽  
Betula Lenta

AbstractThe North American Betula lenta L. (sweet birch) has been used for medicinal reasons for centuries by native Americans. Although sophisticated technologies have rapidly been developed, a large information gap has been observed regarding genetic regulators of medicinally important compounds in sweet birch. Very little is known on the different genes involved in secondary metabolic biosynthesis in sweet birch. To gain a deeper insight into genetic factors, we performed a transcriptome analysis of each three biological samples from different independent trees of sweet and European silver birch (B. pendula Roth). This allowed us to precisely quantify the transcripts of about 24,000 expressed genes including 29 prominent candidate genes putatively involved in the biosynthesis of secondary metabolites like terpenoids, and aromatic benzoic acids. A total number of 597 genes were differentially expressed between B. lenta and B. pendula, while 264 and 210 genes showed upregulation in the bark and leaf of B. lenta, respectively. Moreover, we identified 39 transcriptional regulatory elements, involved in secondary metabolite biosynthesis, upregulated in B. lenta. Our study demonstrated the potential of RNA sequencing to identify candidate genes interacting in secondary metabolite biosynthesis in sweet birch. The candidate genes identified in this study could be subjected to genetic engineering to functionally characterize them in sweet birch. This knowledge can be beneficial to the increase of therapeutically important compounds.

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