Production Of Secondary Metabolites Research Articles

L-DOPA ELICITATION THROUGH CALCIUM ION MEDIATED CHANNEL IN CALLUS CULTURES OF MUCUNA PRURIENS

Objective: The production of L-Dopa in callus cultures of Mucuna pruriens is influenced by substances that regulate calcium channels. Methods: M. pruriens seeds were gathered from the Western Ghats area in Tamil Nadu. L-Dopa was obtained by the Brain (1976) method, A. niger cultures were used for fungal elicitor preparation, and the assay of Ca2+ATPase was studied. Results: The use of fungal triggers resulted in increased L-Dopa levels on the 9th day but reduced levels on the 24th day of culture. When calcium channel modulators like verapamil and chlorpromazine were added, it decreased the growth of calli and L-Dopa production, suggesting the role played by calcium ion channels in L-Dopa synthesis. The calcium ionophore A23187 enhanced calli growth and L-Dopa production, increasing Ca2+ATPase activity. Particularly on the 12th d, Ca2+ATPase was notably active, while the presence of calcium ionophore boosted L-Dopa biosynthesis. Conclusion: The use of fungal elicitors in in vitro cultures of Mucuna pruriens is recommended as a potential method to increase the production of secondary metabolites.

Genomic analysis of secondary metabolite biosynthesis gene clusters and structural characterization of terpene synthase and cytochrome P450 enzymes in Zingiber officinale Roscoe

This study uses bioinformatics approaches to elucidate the genetic basis of secondary metabolite biosynthesis in Zingiber officinale (Z. officinale). To this end, it identifies 44 secondary metabolite biosynthetic gene clusters and maps onto individual chromosomes, with chromosomes 1A and 8A exhibiting higher concentrations. Here, protein homology modeling provided insights into the structural characteristics of terpene synthases and Cytochrome P450 enzymes, shedding light on their potential roles in stress response and secondary metabolite production. Moreover, the identification of enzymes, such as (-)-kolavenyl diphosphate synthase TPS28 and cytochrome P450 93A3-like, opens up new possibilities for investigating the intricate pathways involved in terpene diversity and stress response mechanisms within Z. officinale. This study highlights the importance of understanding the molecular mechanisms underlying plant-derived bioactive compounds for pharmaceutical applications.

In Situ Raman Hyperspectral Analysis of Microbial Colonies for Secondary Metabolites Screening.

Since the discovery of penicillin, a vast array of microbial antibiotics has been identified and applied in the medical field. Globally, the search for drug candidates via microbial screening is ongoing. Traditional screening methods, however, are time-consuming and require labor-intensive sample processing, significantly reducing throughput. This research introduces a Raman spectroscopy-based screening system tailored to the in situ analysis of microbial colonies on solid culture media. Employing multivariate curve resolution-alternating least-squares (MCR-ALS) for spectral decomposition, our approach reveals the production of secondary metabolites at the single colony level. We enhanced the microbial culture method, enabling direct, high signal-to-noise (S/N) ratio Raman spectroscopic measurements of colonies of Escherichia coli and actinomycetes species. Through semisupervised MCR analysis using the known spectra of actinorhodin and undecylprodigiosin as references, we accurately assessed the production of these compounds by Streptomyces coelicolor A3(2). Furthermore, we herein successfully detected the production of amphotericin B by Streptomyces nodosus, even in the absence of prior spectral information. This demonstrates the potential of our technique in the discovery of secondary metabolites. In addition to enabling the detection of the above-mentioned compounds, this analysis revealed the heterogeneity of the spatial distribution of their production in each colony. Our technique makes a significant contribution to the advancement of microbial screening, offering a rapid, efficient alternative to conventional methods and opening avenues for secondary metabolites discovery.

A Review of Laboratory Requirements to Culture Lichen Mycobiont Species.

Lichens are symbiotic associations between fungi (the mycobiont) and algae or cyanobacteria (the photobionts). They synthesize a large number of secondary metabolites, many of which are potential sources of novel molecules with pharmacological and industrial applications. The advancement of in vitro culture methods of lichen-forming fungi would allow the comprehensive application of these compounds at large scales, enable improvements in the synthesis, facilitate understanding of the role of the partners in the synthesis of these compounds and increase our knowledge about the genes associated with secondary metabolites production. The aim of this work is to summarize the nutritional and physicochemical requirements that have been used to date to culture different lichen-forming fungi species. In total, the requirements for the cultivation of 110 species are presented. This review can provide a starting point for future experiments and help advance the methods of culturing lichenized fungi. The type of diaspore selected to isolate the mycobiont, the composition of the isolation and culture media and the corresponding physicochemical parameters are essential in designing an efficient lichen culture system, allowing the achievement of a suitable growth of lichen-forming fungi and the subsequent production of secondary metabolites.

Whole genome–based comparative analysis of the genus Streptomyces reveals many misclassifications

Streptomyces species are experts in the production of bioactive secondary metabolites; however, their taxonomy has fallen victim of the tremendous interest shown by the scientific community, evident in the discovery of numerous synonymous in public repositories. Based on genomic data from NCBI Datasets and nomenclature from the LPSN database, we compiled a dataset of 600 Streptomyces species along with their annotations and metadata. To pinpoint the most suitable taxonomic classification method, we conducted a comprehensive assessment comparing multiple methodologies, including analysis of 16S rRNA, individual housekeeping genes, multilocus sequence analysis (MLSA), and Fast Average Nucleotide Identity (FastANI) on a subset of 409 species with complete data. Due to insufficient resolution of 16S rRNA and inconsistency observed in individual housekeeping genes, we performed a more in-depth analysis, comparing only FastANI and MLSA, which expanded our dataset to include 502 species. With FastANI validated as the preferred method, we conducted pairwise analysis on the entire dataset identifying 59 non-unique species among the 600, and subsequently refined the dataset to 541 unique species. Additionally, we collected data on 724 uncharacterized Streptomyces strains to investigate the uniqueness potential of the unannotated fraction of the Streptomyces genus. Utilizing FastANI, 289 strains could be successfully classified into one of the 541 Streptomyces species.Key points• Evaluation of taxonomic classification methods for Streptomyces species.• Whole genome analysis, specifically FastANI, has been chosen as preferred method.• Various reclassifications are proposed within the Streptomyces genus.Graphical abstract

Harnessing nature's defenders: unveiling the potential of microbial consortia for plant defense induction against Alternaria blight in cumin.

Present study was aimed to develop an efficient microbial consortium for combating Alternaria blight disease in cumin. The research involved isolating biocontrol agents against Alternaria burnsii, characterizing their biocontrol and growth promotion traits, and assessing compatibility. A pot experiment was conducted during rabi season of 2022-2023 to evaluate the bioefficacy of four biocontrol agents (1F, 16B, 31B, and 223B) individually and in consortium, focusing on disease severity, plant growth promotion, and defense responses in cumin challenged with A. burnsii. Microbial isolates 1F, 16B, 31B, and 223B significantly inhibited A. burnsii growth in dual plate assays (~ 86%), displaying promising biocontrol and plant growth promotion activities. They were identified as Trichoderma afroharzianum 1F, Aneurinibacillus aneurinilyticus 16B, Pseudomonas lalkuanensis 31B, and Bacillus licheniformis 223B, respectively. The excellent compatibility was observed among all selected biocontrol agents. Cumin plants treated with consortia of 1F + 16B + 31B + 223B showed least percent disease index (32.47%) and highest percent disease control (64.87%). Consortia of biocontrol agents significantly enhanced production of secondary metabolites (total phenol, flavonoids, antioxidant, and tannin) and activation of antioxidant-defense enzymes (POX, PPOX, CAT, SOD, PAL, and TAL) compared to individual biocontrol treatment and infected control. Moreover, consortium treatments effectively reduced electrolyte leakage over the individual biocontrol agent and infected control treatment. The four-microbe consortium significantly enhanced chlorophyll (154%), carotenoid content (88%), plant height (78.77%), dry weight (72.81%), and seed yield (104%) compared to infected control. Based on these findings, this environmentally friendly four-microbe consortium may be recommended for managing Alternaria blight in cumin.

The role of yeast propagation aeration for subsequent primary fermentation with respect to performance and aroma development

SummaryDuring the primary fermentation of beer, the yeast simultaneously carries out a series of processes such as cell growth, pH shift, and the formation and degradation of essential flavour components. Harvested yeast from a previous fermentation can be used to inoculate the fermentation or fresh cells can be produced through aerobic propagation. This study investigated the influence of different aeration conditions during Saccharomyces pastorianus ssp. carlsbergensis propagation on the cell count development and the production of secondary metabolites during the subsequent primary beer fermentation. Propagations were conducted by applying six different dissolved oxygen concentrations, and the cells were used as inoculum for the subsequent fermentation. Cell count, pH shift, and the development of key aroma compounds were monitored throughout the primary fermentation to evaluate any difference between the conducted fermentations. The outcomes revealed significant distinctions between fermentations using yeast propagated under elevated oxygen levels and those propagated under reduced oxygen levels. Cells propagated using lower oxygen concentrations showed earlier cell growth with 40% lower final cell counts, resulting in 50% reduced biomass yields. Additionally, lower oxygen concentrations during propagation led to lower pH shifts during primary fermentation with 20% more higher alcohols and elevated formation of acetaldehyde, and esters.

Drought stress enhances phytochemical, antioxidant, antidiabetic and anticancer properties in Pandanus tectorius

Global warming is responsible for increasing temperatures and reducing rainfall in many regions of the world. Due to insufficient rainfall or lack of water in the soil, plants experience a range of morphological and biochemical alterations when they are exposed to drought conditions. Interestingly, the cells of drought-stressed plants can serve as a potential source for discovering new drugs. These secondary metabolic products have important biological functions that determine how plants interact with the environment and help them accommodate alterations. Present research has shed light on the response of Pandanus tectorius induced drought stress at 8th and 16th days. The studies observed the levels of various secondary metabolites in plants under drought-induced stress. Among the secondary metabolites analyzed, total alkaloids exhibited the highest overall concentration at 26.19 ± 0.83a. Furthermore, the observations found that drought stress had a significant impact on the plant's secondary metabolism. This resulted in increased levels of total alkaloids, saponins, tannins, and phenolics compared to the control plant. Especially the concentration of phenolics showed the most significant increase, with a remarkable 64.99% rise observed at the 16th day of treatment. The concentration of phenolics reached (20.52 ± 0.181c) at this level. Moreover, compared to control, P. tectorius exhibits significant antioxidant, antidiabetic, anti-inflammatory, molecular docking, and anticancer effects against MDA-MB-231 human breast cancer cell line inhibitory concentration IC50 values (48.91 ± 0.95 μg/mL) at 16th day treated plants. Consequently, the positive responses of P. tectorius drought stress enhance secondary metabolites. This research focus on drought stress stimulus prompts an urge in the production of secondary metabolites in P. tectorius, leading to an increase in its anticancer and anti-diabetic properties and treatments for type-2 diabetes and against fighting for cancer with minimal side effects and helping prevent diseases.

A protocol for the development and maintenance of Coffea arabica (L.) cell suspension cultures

Coffea spp. are remarkable sources of phytochemicals, but the lack of a well-defined culture medium aimed at the induction of non-embryogenic and friable callus hampers the establishment of plant cell suspension cultures for large-scale production of valuable compounds. In this paper, we describe a one-medium protocol suitable to obtain both callus and cell suspension cultures from leaves of two elite cultivars of C. arabica. The protocol was developed through an iterative process involving the determination of the best concentration of auxin and cytokinin, their optimal ratio, as well as the most effective molecule of either hormone class. Young leaves were found to be a good and easy-to-use explant source for callus induction and proliferation, provided that a cytokinin was present in association with a chlorinated auxin in a full strength, semi-solid MS medium. The best results were obtained by hormone concentration and combination of 1 mg/L of both kinetin and 2,4,5-trichlorophenoxyacetic acid. The same ratio of these growth regulators was conveniently used for the development and stabilization of cell suspension cultures in liquid MS medium. When grown in darkness, stabilized suspension cultures showed a fine and homogeneous texture, with a 10-fold biomass increase within 25 days and a cell viability > 90%. In addition, the phytochemical profile revealed the presence of the most widely studied coffee compounds. The protocol can be applied to obtain adequate amounts of cell biomass for use in physiological studies concerning the production of secondary metabolites.

Functional connexion of bacterioferritin in antibiotic production and morphological differentiation in Streptomyces coelicolor

BackgroundSeveral two-component systems of Streptomyces coelicolor, a model organism used for studying antibiotic production in Streptomyces, affect the expression of the bfr (SCO2113) gene that encodes a bacterioferritin, a protein involved in iron storage. In this work, we have studied the effect of the deletion mutant ∆bfr in S. coelicolor.ResultsThe ∆bfr mutant exhibits a delay in morphological differentiation and produces a lesser amount of the two pigmented antibiotics (actinorhodin and undecylprodigiosin) compared to the wild type on complex media. The effect of iron in minimal medium was tested in the wild type and ∆bfr mutant. Consequently, we also observed different levels of production of the two pigmented antibiotics between the two strains, depending on the iron concentration and the medium (solid or liquid) used. Contrary to expectations, no differences in intracellular iron concentration were detected between the wild type and ∆bfr mutant. However, a higher level of reactive oxygen species in the ∆bfr mutant and a higher tolerance to oxidative stress were observed. Proteomic analysis showed no variation in iron response proteins, but there was a lower abundance of proteins related to actinorhodin and ribosomal proteins, as well as others related to secondary metabolite production and differentiation. Additionally, a higher abundance of proteins related to various types of stress, such as respiration and hypoxia among others, was also revealed. Data are available via ProteomeXchange with identifier PXD050869.ConclusionThis bacterioferritin in S. coelicolor (Bfr) is a new element in the complex regulation of secondary metabolism in S. coelicolor and, additionally, iron acts as a signal to modulate the biosynthesis of active molecules. Our model proposes an interaction between Bfr and iron-containing regulatory proteins. Thus, identifying these interactions would provide new information for improving antibiotic production in Streptomyces.

Exiguobacterium acetylicum Strain SI17: A Potential Biocontrol Agent against Peronophythora litchii Causing Post-Harvest Litchi Downy Blight

Litchi downy blight (LDB) caused by Peronophythora litchii destroys 20–30% of litchi fruit every year and causes significant economic losses. Some Exiguobacterium strains exhibit considerable promise in both agricultural and industrial sectors. E. acetylicum SI17, isolated from the litchi fruit carposphere, demonstrated significant biocontrol activity against LDB through pre-harvest treatment. To elucidate its underlying regulatory mechanisms, the genome of SI17 was sequenced and analyzed, revealing a circular chromosome spanning 3,157,929 bp and containing 3541 protein-coding genes and 101 RNA genes. Notably, 94 genes were implicated in the production of secondary metabolites. Among the 29 Exiguobacterium strains so far sequenced, SI17 possessed the largest genome. In the phylogenomic analysis encompassing the entire genome, SI17 was clustered into Group I. Treating litchi fruit with SI17 before harvesting resulted in a decrease in H2O2 content in the fruit peel and an increase in superoxide dismutase activity, thus enhancing resistance to LDB. Interestingly, SI17 did not display plate antagonism against Peronophythora litchii SC18. It can be inferred that SI17 generates secondary metabolites, which enhance litchi’s resistance to LDB. This study represents the first documentation of an Exiguobacterium strain exhibiting a role in litchi plant disease and showcasing significant potential for the biological control of LDB.

Boosting banana resilience: Calcium supplementation enhances osmolyte and secondary metabolites production and strengthens the antioxidant machinery in drought and cold-exposed banana plants

Banana (Musa spp.) is a vital tropical fruit crop cultivated worldwide and is known for its nutritional value. The cultivation of bananas is often challenged by environmental stresses such as cold and drought, which can adversely affect plant productivity. In response to these challenges, plants deploy adaptive mechanisms to mitigate the impacts of environmental stresses. Calcium (Ca2+), recognized as a universal second messenger, is pivotal in cellular responses to hormones, pathogens, and stress factors. This study explores the potential of exogenous calcium supplementation as a cost-effective and promising solution, influencing metabolic activities and signal transductions in plants. To investigate the defensive role of Ca2+ supplementation in banana plants subjected to drought (200 mM Mannitol) and cold (14 °C) stress, comprehensive analyses were conducted to elucidate the mechanism underlying Ca2+-mediated stress tolerance. The plants were treated with mannitol, cold or Hoagland, and then supplemented with CaCl2 (15 mM). Exogenous Ca2+ treatment significantly increased the proline content and maintained water balance and cellular stability. Additionally, it enhanced the production of protective secondary metabolites and activated key antioxidant enzymes, countering oxidative stress. Molecular analysis revealed an upregulation of calcium-binding proteins involved in stress response, while Ca2+ treatment reduced lipid peroxidation, as indicated by lower malondialdehyde (MDA) levels, signifying improved membrane integrity and reduced oxidative damage. These findings underscore the protective impact of exogenously supplied calcium, offering insights for sustainable strategies to enhance banana resilience in the face of environmental challenges and climate change.

Research progress on inhibitors and inhibitory mechanisms of mycotoxin biosynthesis.

Mycotoxins are secondary metabolites produced by fungi with harmful effects such as carcinogenicity, teratogenicity, nephrotoxicity, and hepatotoxicity. They cause widespread contamination of plant products such as crops, food, and feed, posing serious threats to the life and health of human beings and animals. It has been found that many traditionally synthesized and natural compounds are capable of inhibiting the growth of fungi and their secondary metabolite production. Natural compounds have attracted much attention due to their safety, environmental, and health friendly features. In this paper, compounds of plant origin with inhibitory effects on ochratoxins, aflatoxins, Fusarium toxins, and Alternaria toxins, including cinnamaldehyde, citral, magnolol, eugenol, pterostilbene, curcumin, and phenolic acid, are reviewed, and the inhibitory mechanisms of different compounds on the toxin production of fungi are also elucidated, with the aim of providing application references to reduce the contamination of fungal toxins, thus safeguarding the health of human beings and animals.

Core microbes in Cordyceps militaris sclerotia and their nitrogen metabolism-related ecological functions.

The model Cordyceps species Cordyceps militaris is rich in therapeutic compounds. It has recently been demonstrated that symbiotic microbes in sclerotia affect Cordyceps' growth, development, and secondary metabolite production. In this study, core microbes were identified based on C. militaris sclerotia samples obtained from the same site over 5 years. Additionally, bacterial strains isolated from C. militaris sclerotia were found to affect metabolite production and nitrogen utilization, based on functional tests. Moreover, based on the bacterial nitrogen metabolism capacity in the sclerotia and its influence on C. militaris metabolite production, we deduced that bacteria in the sclerotia can indirectly affect C. militaris metabolite production by regulating nitrogen metabolism. This is the first report on how bacteria in the sclerotia affect C. militaris metabolite production from the perspective of the nitrogen cycle. The results increase our understanding of microbial functions in C. militaris sclerotia.

Pseudomonas fluorescens in plant growth promotion and biocontrol: A focus on secondary metabolites, IAA, and siderophores

Pseudomonas fluorescens, a Gram-negative bacterium abundant in soil, plays a critical role in promoting plant growth and controlling pathogens, demonstrating remarkable biocontrol capabilities. This review explores the utility of P. fluorescens and its ability to produce secondary metabolites, IAA (Indole-3-acetic acid), and siderophores, addressing agricultural challenges under the strains of climate change. It emphasizes its role as a plant growth-promoting bacterium (PGPB), synthesizing recent findings on its contributions to enhancing plant resilience, pathogen resistance, and sustainable agricultural practices. The production of secondary metabolites, IAA, and siderophores by P. fluorescens is examined for its effectiveness in biocontrol, nutrient mobilization, and hormonal regulation. These functions are critically analyzed through diverse research methodologies, including laboratory and field trials, underscoring the bacterium’s pivotal role in advancing agricultural sustainability and productivity. As the agricultural sector increasingly focuses on bio-products and the exploration of soil microorganisms, P. fluorescens emerges as a promising solution to enhance farming resilience in the face of climatic adversities.

Elicitor-enhanced steroidal sapogenin accumulation in hairy root cultures of Trigonella foenum-graecum

In current work, we studied hairy root induction in Trigonella foenum graecum, which is an important medicinal plant, and examined the impact of different elicitors on some phytochemical characteristics and metabolites production in hairy root cultures. Accordingly, some factors such as five strain types of Agrobacterium rhizogenes (1724, 15834, A4, A13 and MSU) and three different explants, namely leaf, cotyledon and hypocotyl were studied. The results showed that different A. rhizogenes strains exhibited different infection efficiency. MSU and 15834 had highest efficiency of hairy root induction than other strains. Also, hairy root induction frequency in leaf explants was higher than in other explants. Salicylic acid (SA), nitric oxide (NO), CaCl2 and penconazole (PEN) were used in elicitation process. Hairy roots were treated with SA (0.1 and 0.5 mM), NO (10 and 50 µM), CaCl2 (5 and 10 mM) and PEN (5 and 10 mg/L). Applied elicitors enhanced antioxidant enzymes activities and reduced oxidative stress markers; this observation might be ascribed to regulation of the oxidative status of the elicited cells. Significant increase of antioxidant metabolites (total phenol, flavonoid and anthocyanin) in PEN-treated hairy roots was associated to phenylalanine ammonia lyase activity, indicating an up-regulation of phenylpropanoid/flavonoid metabolism. PEN and CaCl2 treatment enhanced steroidal sapogenin in hairy root cultures. These results suggested that use of elicitors can enhance the production of secondary metabolites in transformed hairy roots. Among the elicitors applied, CaCl2 and PEN were the most effective in increasing secondary metabolite production in transformed hairy roots of T. foenum graecum.

Exploring Microbial Dynamics: The Interaction between Yeasts and Acetic Acid Bacteria in Port Wine Vinegar and Its Implications on Chemical Composition and Sensory Acceptance

Port wine vinegar, a product of the esteemed Port wine, is renowned for its intricate blend of flavors and aromas, a result of complex microbial interactions. This study delves into the fascinating world of yeast and acetic acid bacteria (AAB) interactions during fermentation, which significantly influence the vinegar’s chemical composition and sensory properties. We specifically investigate the role of yeasts in fermenting sugars into ethanol, a process that AAB then converts into acetic acid. The impact of these interactions on the production of secondary metabolites, such as gluconic acid, ketones, aldehydes, and esters, which contribute to the vinegar’s unique sensory profile, is thoroughly examined. Advanced analytical techniques, including GC-MS and e-nose technology, alongside sensory evaluation, are employed to assess these effects. The research underscores the significance of ethanol tolerance in AAB and other production challenges in determining vinegar quality and underscores the importance of optimizing fermentation conditions and sustainable practices. The findings of this study underscore the importance of strain interactions and production techniques, which can significantly enhance the quality and market appeal of Port wine vinegar, providing valuable insights for the industry. This review also identifies exciting and critical areas for future research, inspiring further exploration and proposing strategies for advancing production and application in culinary, health, and industrial contexts.

Genome analysis of the esca-associated Basidiomycetes Fomitiporia mediterranea, Fomitiporia polymorpha, Inonotus vitis, and Tropicoporus texanus reveals virulence factor repertoires characteristic of white-rot fungi.

Some Basidiomycete fungi are important plant pathogens, and certain species have been associated with the grapevine trunk disease esca. We present the genomes of 4 species associated with esca: Fomitiporia mediterranea, Fomitiporia polymorpha, Tropicoporus texanus, and Inonotus vitis. We generated high-quality phased genome assemblies using long-read sequencing. The genomic and functional comparisons identified potential virulence factors, suggesting their roles in disease development. Similar to other white-rot fungi known for their ability to degrade lignocellulosic substrates, these 4 genomes encoded a variety of lignin peroxidases and carbohydrate-active enzymes (CAZymes) such as CBM1, AA9, and AA2. The analysis of gene family expansion and contraction revealed dynamic evolutionary patterns, particularly in genes related to secondary metabolite production, plant cell wall decomposition, and xenobiotic degradation. The availability of these genomes will serve as a reference for further studies of diversity and evolution of virulence factors and their roles in esca symptoms and host resistance.

Genome Mining of Pseudanabaena galeata CCNP1313 Indicates a New Scope in the Search for Antiproliferative and Antiviral Agents.

Compounds derived from natural sources pave the way for novel drug development. Cyanobacteria is an ubiquitous phylum found in various habitats. The fitness of those microorganisms, within different biotopes, is partially dependent on secondary metabolite production. Their enhanced production under biotic/abiotic stress factors accounts for better survival rates of cells, and thereby cyanobacteria are as an enticing source of bioactive compounds. Previous studies have shown the potent activity of extracts and fractions from Pseudanabaena galeata (Böcher 1949) strain CCNP1313 against cancer cells and viruses. However, active agents remain unknown, as the selected peptides had no effect on the tested cell lines. Here, we present a bottom-up approach, pinpointing key structures involved in secondary metabolite production. Consisting of six replicons, a complete genome sequence of P. galeata strain CCNP1313 was found to carry genes for non-ribosomal peptide/polyketide synthetases embedded within chromosome spans (4.9 Mbp) and for a ribosomally synthesized peptide located on one of the plasmids (0.2 Mbp). Elucidation of metabolite synthesis pathways led to prediction of their structure. While none of the synthesis-predicted products were found in mass spectrometry analysis, unexplored synthetases are characterized by structural similarities to those producing potent bioactive compounds.

Involvement of LaeA and Velvet Proteins in Regulating the Production of Mycotoxins and Other Fungal Secondary Metabolites.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical, and food importance, such as mycotoxins, antibiotics, and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expressions that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition of the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulate production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.