scholarly journals Discovery of Novel Glycerolated Quinazolinones from Streptomyces sp. MBT27

2018 ◽  
Author(s):  
Nataliia Machushynets ◽  
Changsheng Wu ◽  
Somayah S. Elsayed ◽  
Thomas Hankemeier ◽  
Gilles P. van Wezel
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Secondary Metabolite ◽  
Anthranilic Acid ◽  
Growth Conditions ◽  
Secondary Metabolite Production ◽  
Streptomyces Sp ◽  
Metabolite Production ◽  
Bioactive Natural Products ◽  
Interesting Family

AbstractActinobacteria are a major source of novel bioactive natural products. A challenge in the screening of these microorganisms lies in finding the favorable growth conditions for secondary metabolite production and dereplication of known molecules. Here, we report that Streptomyces sp. MBT27 produces 4-quinazolinone alkaloids in response to elevated levels of glycerol, whereby quinazolinones A (1) and B (2) form a new sub-class of this interesting family of natural products. Global Natural Product Social molecular networking (GNPS) resulted in a quinazolinone-related network that included anthranilic acid (3), anthranilamide (4), 4(3H)-quinazolinone (5) and 2,2-dimethyl-1,2-dihydroquinazolin-4(3H)-one (6). Actinomycins D (7) and X2 (8) were also identified in the extracts of Streptomyces sp. MBT27. The induction of quinazolinone production by glycerol combined with biosynthetic insights provide evidence that glycerol is integrated into the chemical scaffold. The unprecedented 1,4-dioxepane ring that is spiro-fused into the quinazolinone backbone, is most likely formed by intermolecular etherification of two units of glycerol. Our work underlines the importance of varying the growth conditions for the discovery of novel natural products and for understanding their biosynthesis.

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.

scholarly journals Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production

2018 ◽  
Vol 9 (38) ◽  
pp. 7510-7519 ◽  
Author(s):  
Fu Yan ◽  
Christian Burgard ◽  
Alexander Popoff ◽  
Nestor Zaburannyi ◽  
Gregor Zipf ◽  
...  
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Secondary Metabolite ◽  
Combinatorial Biosynthesis ◽  
Secondary Metabolite Production ◽  
Metabolite Production

Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products.

scholarly journals Effective Production of Aromatic Polyketides in Streptomyces using a Combined-Culture Method

2016 ◽  
Vol 11 (7) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Shotaro Hoshino ◽  
Masahiro Okada ◽  
Hiroyasu Onaka ◽  
Ikuro Abe
Keyword(s):  
Secondary Metabolite ◽  
Spectroscopic Analysis ◽  
Culture Method ◽  
Mycolic Acid ◽  
Secondary Metabolite Production ◽  
Streptomyces Sp ◽  
Metabolite Production ◽  
Aromatic Polyketides ◽  
Fermentation Method

Combined-culture is a fermentation method which efficiently induces secondary metabolite production in Streptomyces by co-culturing them with mycolic acid-containing bacteria. As a result of combined-culture screening of our terrestrial Streptomyces collection using UV-HPLC, one of the tested strains, Streptomyces sp. TAKO-2, produced two known aromatic polyketides, julichrome Q6 (1) and julichrome Q8·8 (2), when co-cultured with the mycolic acid-containing bacterium Tsukamurella pulmonis TP-B0596. The structures of 1 and 2 were confirmed by spectroscopic analysis and literature data.

scholarly journals The impact of bZIP Atf1ortholog global regulators in fungi

2021 ◽  
Author(s):  
Éva Leiter ◽  
Tamás Emri ◽  
Klaudia Pákozdi ◽  
László Hornok ◽  
István Pócsi
Keyword(s):  
Transcription Factors ◽  
Stress Response ◽  
Secondary Metabolite ◽  
Plant Pathogens ◽  
Leucine Zipper ◽  
Secondary Metabolite Production ◽  
Special Focus ◽  
Human Pathogens ◽  
Metabolite Production ◽  
The Impact

Abstract Regulation of signal transduction pathways is crucial for the maintenance of cellular homeostasis and organismal development in fungi. Transcription factors are key elements of this regulatory network. The basic-region leucine zipper (bZIP) domain of the bZIP-type transcription factors is responsible for DNA binding while their leucine zipper structural motifs are suitable for dimerization with each other facilitiating the formation of homodimeric or heterodimeric bZIP proteins. This review highlights recent knowledge on the function of fungal orthologs of the Schizosaccharomyces pombe Atf1, Aspergillus nidulans AtfA, and Fusarium verticillioides FvAtfA, bZIP-type transcription factors with a special focus on pathogenic species. We demonstrate that fungal Atf1-AtfA-FvAtfA orthologs play an important role in vegetative growth, sexual and asexual development, stress response, secondary metabolite production, and virulence both in human pathogens, including Aspergillus fumigatus, Mucor circinelloides, Penicillium marneffei, and Cryptococcus neoformans and plant pathogens, like Fusarium ssp., Magnaporthe oryzae, Claviceps purpurea, Botrytis cinerea, and Verticillium dahliae. Key points • Atf1 orthologs play crucial role in the growth and development of fungi. • Atf1 orthologs orchestrate environmental stress response of fungi. • Secondary metabolite production and virulence are coordinated by Atf1 orthologs.

scholarly journals Advances and Perspectives in Tissue Culture and Genetic Engineering of Cannabis

2021 ◽  
Vol 22 (11) ◽  
pp. 5671
Author(s):  
Mohsen Hesami ◽  
Austin Baiton ◽  
Milad Alizadeh ◽  
Marco Pepe ◽  
Davoud Torkamaneh ◽  
...  
Keyword(s):  
Plant Regeneration ◽  
Genetic Engineering ◽  
Suspension Culture ◽  
Secondary Metabolite ◽  
Hairy Root ◽  
Root Culture ◽  
Hairy Root Culture ◽  
Gene Transformation ◽  
Secondary Metabolite Production ◽  
Metabolite Production

For a long time, Cannabis sativa has been used for therapeutic and industrial purposes. Due to its increasing demand in medicine, recreation, and industry, there is a dire need to apply new biotechnological tools to introduce new genotypes with desirable traits and enhanced secondary metabolite production. Micropropagation, conservation, cell suspension culture, hairy root culture, polyploidy manipulation, and Agrobacterium-mediated gene transformation have been studied and used in cannabis. However, some obstacles such as the low rate of transgenic plant regeneration and low efficiency of secondary metabolite production in hairy root culture and cell suspension culture have restricted the application of these approaches in cannabis. In the current review, in vitro culture and genetic engineering methods in cannabis along with other promising techniques such as morphogenic genes, new computational approaches, clustered regularly interspaced short palindromic repeats (CRISPR), CRISPR/Cas9-equipped Agrobacterium-mediated genome editing, and hairy root culture, that can help improve gene transformation and plant regeneration, as well as enhance secondary metabolite production, have been highlighted and discussed.

Sign in / Sign up

Export Citation Format

Share Document