Effect of Butyrolactone I on the Producing Fungus,Aspergillus terreus

1998 ◽  
Vol 64 (10) ◽  
pp. 3707-3712 ◽  
Author(s):  
Timothy G. Schimmel ◽  
Allen D. Coffman ◽  
Sarah J. Parsons

ABSTRACT Butyrolactone I [α-oxo-β-(p-hydroxyphenyl)-γ-(p-hydroxy-m-3,3-dimethylallyl-benzyl)-γ-methoxycarbonyl-γ-butyrolactone] is produced as a secondary metabolite by Aspergillus terreus. Because small butyrolactone-containing molecules act as self-regulating factors in some bacteria, the effects of butyrolactone I on the producing organism were studied; specifically, changes in morphology, sporulation, and secondary metabolism were studied. Threefold or greater increases in hyphal branching (with concomitant decreases in the average hyphal growth unit), submerged sporulation, and secondary metabolism were observed when butyrolactone I was added to cultures of A. terreus. Among the secondary metabolites whose production was increased by this treatment was the therapeutically important compound lovastatin. These findings indicate that butyrolactone I induces morphological and sporulation changes inA. terreus and enhances secondary metabolite production in a manner similar to that previously reported for filamentous bacteria.

2012 ◽  
Vol 10 (2) ◽  
pp. 120 ◽  
Author(s):  
Risa Nofiani

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


2015 ◽  
Vol 12 ◽  
pp. 35-41 ◽  
Author(s):  
Huiqin Chen ◽  
Georgios Daletos ◽  
Mohamed S. Abdel-Aziz ◽  
Dhana Thomy ◽  
Haofu Dai ◽  
...  

2021 ◽  
Author(s):  
Krishna Kumar Rai ◽  
Nagendra Rai ◽  
Shashi Pandey-Rai

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.


2021 ◽  
Vol 2 ◽  
Author(s):  
Trong T. Dao ◽  
Kate M. J. de Mattos-Shipley ◽  
Ian M. Prosser ◽  
Katherine Williams ◽  
Marija K. Zacharova ◽  
...  

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.


Author(s):  
Tuncay Çalışkan ◽  
Rüştü Hatipoğlu ◽  
Saliha Kırıcı

Plant secondary metabolites are a group of organic compounds produced by plants to interact with biotic and abiotic factors and for the establishment of defence mechanism. Secondary metabolites are classified based on their biosynthetic origin and chemical structure. They have been used as pharmaceutical, agrochemical, flavours, fragrances, colours and food additives. Secondary metabolites are traditionally produced from the native grown or field grown plants. However, this conventional approach has some disadvantages such as low yield, instability of secondary metabolite contents of the plants due to geographical, seasonal and environmental variations, need for land and heavy labour to grow plants. Therefore, plant cell and organ cultures have emerged as an alternative to plant growing under field conditions for secondary metabolite production. In this literature review, present state of secondary metabolite production through plant cell and organ cultures, its problems as well as solutions of the problems were discussed.


2012 ◽  
Vol 7 (6) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Bartholomeu A. Barros-Filho ◽  
Maria C. F. de Oliveira ◽  
Jair Mafezoli ◽  
Francisco G. Barbosa ◽  
Edson Rodrigues-Filho

The basidiomycete Lentinus strigellus was cultivated in three different culture media and the secondary metabolites produced under different culture conditions were isolated and identified. When cultivated in a liquid medium with peptone, L. strigellus afforded the benzopyrans, 2,2-dimethyl-6-methoxychroman-4-one, 4-hydroxy-2,2-dimethyl-6-methoxychromane and (3 R,4 S)-3,4-dihydroxy-2,2-dimethyl-6-methoxychromane. The indole alkaloid echinuline and the anthraquinone fiscione, both unprecedented for the genus Lentinus, were isolated from the mycelium of the fungus. When cultured in Czapek medium enriched with potato broth, the fungus afforded the same benzopyrans except (3 S,4 S)-3,4-dihydroxy-2,2-dimethyl-6-methoxychromane. Panepoxydone and isopanepoxydone were also isolated when the microorganism was grown in Czapek medium.


2018 ◽  
Vol 84 (19) ◽  
Author(s):  
Brett C. Covington ◽  
Jeffrey M. Spraggins ◽  
Audrey E. Ynigez-Gutierrez ◽  
Zachary B. Hylton ◽  
Brian O. Bachmann

ABSTRACT Microorganisms within microbial communities respond to environmental challenges by producing biologically active secondary metabolites, yet the majority of these small molecules remain unidentified. We have previously demonstrated that secondary metabolite biosynthesis in actinomycetes can be activated by model environmental chemical and biological stimuli, and metabolites can be identified by comparative metabolomics analyses under different stimulus conditions. Here, we surveyed the secondary metabolite productivity of a group of 20 phylogenetically diverse actinobacteria isolated from hypogean (cave) environments by applying a battery of stimuli consisting of exposure to antibiotics, metals, and mixed microbial culture. Comparative metabolomics was used to reveal secondary metabolite responses from stimuli. These analyses revealed substantial changes in global metabolomic dynamics, with over 30% of metabolomic features increasing more than 10-fold under at least one stimulus condition. Selected features were isolated and identified via nuclear magnetic resonance (NMR), revealing several known secondary metabolite families, including the tetarimycins, aloesaponarins, hypogeamicins, actinomycins, and propeptins. One prioritized metabolite was identified to be a previously unreported aminopolyol polyketide, funisamine, produced by a cave isolate of Streptosporangium when exposed to mixed culture. The production of funisamine was most significantly increased in mixed culture with Bacillus species. The biosynthetic gene cluster responsible for the production of funisamine was identified via genomic sequencing of the producing strain, Streptosporangium sp. strain KDCAGE35, which facilitated a deduction of its biosynthesis. Together, these data demonstrate that comparative metabolomics can reveal the stimulus-induced production of natural products from diverse microbial phylogenies. IMPORTANCE Microbial secondary metabolites are an important source of biologically active and therapeutically relevant small molecules. However, much of this active molecular diversity is challenging to access due to low production levels or difficulty in discerning secondary metabolites within complex microbial extracts prior to isolation. Here, we demonstrate that ecological stimuli increase secondary metabolite production in phylogenetically diverse actinobacteria isolated from understudied hypogean environments. Additionally, we show that comparative metabolomics linking stimuli to metabolite response data can effectively reveal secondary metabolites within complex biological extracts. This approach highlighted secondary metabolites in almost all observed natural product classes, including low-abundance analogs of biologically relevant metabolites, as well as a new linear aminopolyol polyketide, funisamine. This study demonstrates the generality of activating stimuli to potentiate secondary metabolite production across diverse actinobacterial genera.


2014 ◽  
Vol 9 (7) ◽  
pp. 686-698 ◽  
Author(s):  
Vijay Kumar ◽  
Shailesh Singh ◽  
Rajib Bandopadhyay ◽  
Madan Sharma ◽  
Sheela Chandra

AbstractAn efficient protocol of plant regeneration through direct and indirect organogenesis in Swertia chirayita was developed. Explants cultured on Murashige and Skoog medium supplemented with 2,4-D (0.5 mg L−1) with combination of Kinetin (0.5 mg L−1) showed the highest frequency (84%) of callusing and 1.0mg L−1 6-benzyladenine (BA) in combination with (100 mg L−1) Adenine sulphate (Ads) + (0.1 mg L−1) Indole acetic acid (IAA) was excellent for maximum adventitious shoot (12.69 ± 1.30) formation in four week of culture. A maximum number of (7.14 ± 0.99) shoots were developed per leaf explants through direct organogenesis. The highest frequency of rooting (11.46 ± 1.56) was observed on MS medium augmented with IAA (1.0 mg L−1). Well-rooted shoots transferred to plastic pots containing a soilrite: sand mix and then moved to the greenhouse for further growth and development. Four major secondary metabolites were analyzed and quantified using high performance liquid chromatography. Amount of secondary metabolites was found significantly higher, in in vitro plantlets compared to in vivo plantlets and callus raised from S. chirayita. Higher heavy metal accumulation in in vitro as compared to in vivo plantlets correlates higher secondary metabolite production supporting that they play regulatory role in influencing the plant secondary metabolism.


2020 ◽  
Author(s):  
Balaji Muralikrishnan ◽  
Retnakumar R J ◽  
Ranjit Ramachandran ◽  
Vinodh J S ◽  
Nijisha M ◽  
...  

AbstractConditioning of morphology is an effective technique to enhance secondary metabolite production by Streptomyces. Here we report a novel conditioning method employing glass marbles in batch cultures to enhance secondary metabolite production by Streptomyces sp. The marbles seem to spatially separate aerial and submerged mycelia in the flask which was necessary for the qualitative and quantitative enhancement of metabolite production of secondary metabolites. The method also offers shorter incubation period compared to conventional methods for effective production. Further, using a combination of this method and response surface methodology we could enhance the production of antimycobacterial molecules chrysomycin A and B significantly.ImportanceRediscovery of existing molecules and lack of techniques to induce production of secondary metabolites are the major bottlenecks associated with drug discovery of novel bioactive molecules from Streptomyces, the major source of marketable drugs today. We found a new method to increase the diversity and quantity of secondary metabolites in two Streptomyces species. This method thus enhances the chance of finding novel active principles from Streptomyces.


2019 ◽  
Author(s):  
Sonja L. Knowles ◽  
Matthew E. Mead ◽  
Lilian Pereira Silva ◽  
Huzefa A. Raja ◽  
Jacob L. Steenwyk ◽  
...  

ABSTRACTAspergillus fumigatus is a major opportunistic human pathogen. Multiple traits contribute to A. fumigatus pathogenicity, including its ability to produce specific secondary metabolites, such as gliotoxin. Gliotoxin is known to inhibit the host immune response, and genetic mutants that inactivate gliotoxin biosynthesis (or secondary metabolism in general) attenuate A. fumigatus virulence. The genome of A. fischeri, a very close non-pathogenic relative of A. fumigatus, contains a biosynthetic gene cluster that exhibits high sequence similarity to the A. fumigatus gliotoxin cluster. However, A. fischeri is not known to produce gliotoxin. To gain further insight into the similarities and differences between the major pathogen A. fumigatus and the non-pathogen A. fischeri, we examined whether A. fischeri strain NRRL 181 biosynthesizes gliotoxin and whether its production, and of secondary metabolites more generally, influence its virulence profile. We found that A. fischeri biosynthesizes gliotoxin in the same conditions as A. fumigatus. However, whereas loss of laeA, a master regulator of secondary metabolite production, has been previously shown to reduce the virulence of A. fumigatus, we found that laeA loss (and loss of secondary metabolite production, including gliotoxin) in A. fischeri does not influence its virulence. These results suggest that gliotoxin and secondary metabolite production are virulence factors in the genomic and phenotypic background of the major pathogen A. fumigatus but are much less important in the background of the non-pathogen A. fischeri. We submit that understanding the observed spectrum of pathogenicity across closely related pathogenic and non-pathogenic Aspergillus species will require detailed characterization of their biological, chemical, and genomic similarities and differences.IMPORTANCEAspergillus fumigatus is a major opportunistic fungal pathogen of humans but most of its close relatives are non-pathogenic. Why is that so? This important, yet largely unanswered, question can be addressed by examining how A. fumigatus and its non-pathogenic close relatives are similar or different with respect to virulence-associated traits. We investigated whether Aspergillus fischeri, a non-pathogenic close relative of A. fumigatus, can produce gliotoxin, a mycotoxin known to contribute to A. fumigatus virulence. We discovered that the non-pathogenic A. fischeri produces gliotoxin under the same conditions as the major pathogen A. fumigatus. However, we also discovered that, in contrast to what has been previously observed in A. fumigatus, loss of secondary metabolite, including gliotoxin, production in A. fischeri does not alter its virulence. Our results are consistent with the “cards of virulence” model of opportunistic fungal disease, where the ability to cause disease stems from the combination (“hand”) of individual virulence factors (“cards”), but not from individual factors per se.


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