The Role of LaeA and LovE Regulators in Lovastatin Biosynthesis with Exogenous Polyamines in Aspergillus terreus

Zhgun, A. A.; Nuraeva, Gulgina K.; Eldarov, Michael A.

doi:10.1134/s0003683819060176

Cited by 15 publications

(27 citation statements)

References 31 publications

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“…Moreover, the elevated polyamine pool is essential not only for the survival of the fungi during the mutagenesis, but also for the production of secondary metabolites. For example, the addition of exogenous polyamines (1,3-diaminopropane, Spd) increases the production of penicillin G in Penicillium chrysogenum Wisconsin 54-1255 strain [64], and the biosynthesis of lovastatin in Aspergillus terreus [41,65].…”

Section: Discussionmentioning

confidence: 99%

Hydroxylamine Analogue of Agmatine: Magic Bullet for Arginine Decarboxylase

et al. 2020

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The biogenic polyamines, spermine, spermidine (Spd) and putrescine (Put) are present at micro-millimolar concentrations in eukaryotic and prokaryotic cells (many prokaryotes have no spermine), participating in the regulation of cellular proliferation and differentiation. In mammalian cells Put is formed exclusively from L-ornithine by ornithine decarboxylase (ODC) and many potent ODC inhibitors are known. In bacteria, plants, and fungi Put is synthesized also from agmatine, which is formed from L-arginine by arginine decarboxylase (ADC). Here we demonstrate that the isosteric hydroxylamine analogue of agmatine (AO-Agm) is a new and very potent (IC50 3•10−8 M) inhibitor of E. coli ADC. It was almost two orders of magnitude less potent towards E. coli ODC. AO-Agm decreased polyamine pools and inhibited the growth of DU145 prostate cancer cells only at high concentration (1 mM). Growth inhibitory analysis of the Acremonium chrysogenum demonstrated that the wild type (WT) strain synthesized Put only from L-ornithine, while the cephalosporin C high-yielding strain, in which the polyamine pool is increased, could use both ODC and ADC to produce Put. Thus, AO-Agm is an important addition to the set of existing inhibitors of the enzymes of polyamine biosynthesis, and an important instrument for investigating polyamine biochemistry.

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Section: Discussionmentioning

confidence: 99%

Hydroxylamine Analogue of Agmatine: Magic Bullet for Arginine Decarboxylase

et al. 2020

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Section: Possible Mechanisms Of Influencing Of Exogenous Pas On Sm Prmentioning

confidence: 99%

“…An increase in the production of the target SM by 100-to 1000-fold and the elimination of spin-off products under the fermentation conditions in the improved fungal strains ( Figure 2B) are associated with two main molecular events, the upregulation of genes from target BGC and the knockout of genes from alternative BGC [27,33,41,42]. Since the expression of BGC genes is controlled by the pathway-specific regulation [27,43,44], global regulation [45,46], and global regulation of SM [47][48][49][50], the SCI programs are accompanied by changes in such controls. For instance, during CGI program for penicillin G (PenG) production in HY strain (DS17690) two main events occurred, the shift in global regulation of secondary metabolism by introducing mutations in LaeA and VelA and mutations in key enzymes for spin-off SM [33].…”

Section: The Molecular Mechanisms Of Sm Overproduction In Filamentousmentioning

confidence: 99%

“…In order to confirm this hypothesis we carried out fermentation with PAs for WT, HY and E6 strains of A. terreus [44]. The LOV production in A. terreus is under the control of two major positive regulators, the LovE pathway-specific regulator and LaeA global regulator of fungi SM [44]. The A. terreus E6 strain derived from WT by the genetic engineering introduction the additional copy of lovE gene under the control of constitutive promotor [27].…”

Section: Possible Mechanisms Of Influencing Of Exogenous Pas On Sm Prmentioning

confidence: 99%

“…WT: wild type, E6: OE::lovE, HY: high yielding, and Spd: spermidine. Adapted with permission from [44]. of ODC, the key enzyme of PAs biosynthesis, on minimal agar media [65].…”

Section: The Endogenous Polyamines Content In a Chrysogenum Hy Strainmentioning

confidence: 99%

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Random Mutagenesis of Filamentous Fungi Strains for High-Yield Production of Secondary Metabolites: The Role of Polyamines

Жгун¹

2021

Genotoxicity and Mutagenicity - Mechanisms and Test Methods

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A filamentous fungus (also called molds or moldy fungus) is a taxonomically diverse organism from phylum Zygomycota and Ascomycota with filamentous hyphae and has the ability to produce airborne spores or conidia. Currently, more than 70,000 molds are known, and some of them contain unique and unusual biochemical pathways. A number of products from such pathways, especially, the secondary metabolite (SM) pathways are used as important pharmaceuticals, including antibiotics, statins, and immunodepresants. Under different conditions, the individual species can produce more than 100 SM. The strain improvement programs lead to high yielding in target SM and significant reduction of spin-off products. The main tool for the strain improvement of filamentous fungi is random mutagenesis and screening. The majority of industrial overproducing SM strains were developed with the help of such technique over the past 50–70 years; the yield of the target SM increased by 100- to 1000-fold or more. Moreover, most of the strains have reached their technological limit of improvement. A new round of mutagenesis has not increased overproduction. Recently, it was shown that that the addition of exogenous polyamines may increase the production of such improved strains of filamentous fungi. The possible molecular mechanism of this phenomenon and its biotechnological applications are discussed.

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Genome mining of secondary metabolites from a marine-derived Aspergillus terreus B12

et al. 2021

Arch Microbiol

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As an important saprophytic filamentous fungus, Aspergillus terreus is ubiquitously distributed, including soil rhizospheres and marine environments. Due to the prominent capabilities of bioconversion and biosynthesis, A. terreus has become attractive in biotechnical and pharmaceutical industry. In this work, an A. terreus strain, B12, was isolated from sponge in South China Sea, which demonstrated broad bacteriostatic effects against a variety of pathogenic bacteria. The whole genome was sequenced, showing a genetic richness of BGCs, which might underpin the metabolic plasticity and adaptive resilience for the strain. Genome mining identified 67 biosynthetic gene clusters (BGCs), among which, 6 gene clusters could allocate to known BGCs (100% identity), corresponding to diverse metabolites like clavaric acid, dihydroisoflavipucine /isoflavipucine, dimethylcoprogen, alternariol, aspterric acid and pyranonigrin E. However, instead of the putative compounds, several other products were obtained from the B12 fermentation, including terrein, butyrolactone I, terretonin A&E, acoapetaline B and epi-aszonalenins A. Of note, acoapetaline B and epi-aszonalenins A, discovered natural products recently with little information, unexpectedly were reported in this A. terreus strain. The genomic and heterogeneity observed in strain B12, should be at least partially attributed to the genetic variability and biochemical diversity of A. terreus, which could be an interesting issue open to future efforts.

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The Role of LaeA and LovE Regulators in Lovastatin Biosynthesis with Exogenous Polyamines in Aspergillus terreus

Cited by 15 publications

References 31 publications

Hydroxylamine Analogue of Agmatine: Magic Bullet for Arginine Decarboxylase

Hydroxylamine Analogue of Agmatine: Magic Bullet for Arginine Decarboxylase

Random Mutagenesis of Filamentous Fungi Strains for High-Yield Production of Secondary Metabolites: The Role of Polyamines

Genome mining of secondary metabolites from a marine-derived Aspergillus terreus B12

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