The concentration dynamics of inorganic polyphosphates during the cephalosporin C synthesis by Acremonium chrysogenum

Valiakhmetov, Airat; Trilisenko, L. V.; Vagabov, V. M.; Bartoshevich, Yu. E.; Kulaev, I. S.; Novak, Metka; Domracheva, A. G.; Eldarov, M. A.; Skryabin, K. G.

doi:10.1134/s0003683810020109

Cited by 6 publications

(15 citation statements)

References 15 publications

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“…It would be particularly interesting to study the exopolyphosphatases of antibiotic producers in view of detection of substantial changes in polyP level during the synthesis of antibiotics [1]. It has been shown that the content of low and high molecular weight polyP increas es and decreases, respectively, during cephalosporin biosynthesis in the fungus Acremonium chrysogenum [15]. The yeast exopolyphosphatase PPN1 is more active with high molecular weight polyP than with low molecular weight polyP [12].…”

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confidence: 99%

Polyphosphates and exopolyphosphatase activities in the yeast Saccharomyces cerevisiae under overexpression of homologous and heterologous PPN1 genes

Eldarov

Baranov

Думина

et al. 2013

Biochemistry Moscow

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The role of exopolyphosphatase PPN1 in polyphosphate metabolism in fungi has been studied in strains of Saccharomyces cerevisiae transformed by the yeast PPN1 gene and its ortholog of the fungus Acremonium chrysogenum producing cephalosporin C. The PPN1 genes were expressed under a strong constitutive promoter of the gene of glycerol aldehyde-triphosphate dehydrogenase of S. cerevisiae in the vector pMB1. The yeast strain with inactivated PPN1 gene was transformed by the above vectors containing the PPN1 genes of S. cerevisiae and A. chrysogenum. Exopolyphosphatase activity in the transformant with the yeast PPN1 increased 28- and 11-fold compared to the mutant and parent PPN1 strains. The amount of polyphosphate in this transformant decreased threefold. Neither the increase in exopolyphosphatase activity nor the decrease in polyphosphate content was observed in the transformant with the orthologous PPN1 gene of A. chrysogenum, suggesting the absence of the active form of PPN1 in this transformant.

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confidence: 99%

Polyphosphates and exopolyphosphatase activities in the yeast Saccharomyces cerevisiae under overexpression of homologous and heterologous PPN1 genes

Eldarov

Baranov

Думина

et al. 2013

Biochemistry Moscow

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“…However, along with beneficial changes that increase the production of the target SM, reduce the amount of spin-off products, and others, numerous side changes begin to accumulate in the fungal strain. They can appear in a slow growth on agar and liquid media [27,64,65], a decrease in stress resistance [66], reduction in the conidia formation [64] and many other properties, expressed in a decrease in the overall viability of the strain [66,67]. Finally, the stage comes when the next mutagenic effect no longer leads to further strain improvement.…”

Section: The Technological Limit Of Csi Of Filamentous Fungi For Sm Pmentioning

confidence: 99%

“…The addition of 5 mM α-difluoromethylornithine (DFMO) or 5 mM of 1-aminooxy-3-aminopropane (APA) completely inhibited the growth of the WT strain, unlike HY strain (Figure 4) [65]. Such kind of resistance against inhibiters of key enzyme for PAs production turned out to be rather strange since HY strain is significantly weakened after SCI program [32,61,64,66,67]. The only previously observed advantage over the WT strain was expressed in CPC overproduction [41].…”

Section: The Endogenous Polyamines Content In a Chrysogenum Hy Strainmentioning

confidence: 99%

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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“…Previously we demonstrated the decreased PMA activity in A . chrysogenum HY strain [ 29 , 30 ]. This strain typically produces 9–12 grams of CPC during laboratory fermentation in shake flasks, 200–300 times higher than WT strains [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…We have previously shown that the overproduction phenotype correlates with upregulation of cef genes [ 31 ], chromosomal rearrangements [ 5 ], as well as alterations in polyamine metabolism [ 32 ], in cell wall structure [ 33 ], in size of filamentous hyphae and conidia formation [ 34 ], in colony size and coloration [ 26 ], and has other physiological changes. The PMA1 defect may be one of the reasons for reduced strain growth rate and overall fitness, diminished resistance to abiotic stress and proficiency in nutrients [ 30 ]. So, the question arises as to whether such deficiency in PMA activity can affect the transport of target antibiotics, namely lowering of CPC export and/or decreasing nutrients uptake from the culture medium, thus influencing the strain growth rate.…”

Section: Introductionmentioning

confidence: 99%

The critical role of plasma membrane H+-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum

Zhgun¹,

Думина²,

Valiakhmetov

et al. 2020

PLoS ONE

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The filamentous fungus Acremonium chrysogenum is the main industrial producer of cephalosporin C (CPC), one of the major precursors for manufacturing of cephalosporin antibiotics. The plasma membrane H + -ATPase (PMA) plays a key role in numerous fungal physiological processes. Previously we observed a decrease of PMA activity in A . chrysogenum overproducing strain RNCM 408D (HY) as compared to the level the wild-type strain A . chrysogenum ATCC 11550. Here we report the relationship between PMA activity and CPC biosynthesis in A . chrysogenum strains. The elevation of PMA activity in HY strain through overexpression of PMA1 from Saccharomyces cerevisiae , under the control of the constitutive gpdA promoter from Aspergillus nidulans , results in a 1.2 to 10-fold decrease in CPC production, shift in beta-lactam intermediates content, and is accompanied by the decrease in cef genes expression in the fermentation process; the characteristic colony morphology on agar media is also changed. The level of PMA activity in A . chrysogenum HY OE :: PMA1 strains has been increased by 50–100%, up to the level observed in WT strain, and was interrelated with ATP consumption; the more PMA activity is elevated, the more ATP level is depleted. The reduced PMA activity in A . chrysogenum HY strain may be one of the selected events during classical strain improvement, aimed at elevating the ATP content available for CPC production.

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The concentration dynamics of inorganic polyphosphates during the cephalosporin C synthesis by Acremonium chrysogenum

Cited by 6 publications

References 15 publications

Polyphosphates and exopolyphosphatase activities in the yeast Saccharomyces cerevisiae under overexpression of homologous and heterologous PPN1 genes

Polyphosphates and exopolyphosphatase activities in the yeast Saccharomyces cerevisiae under overexpression of homologous and heterologous PPN1 genes

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

The critical role of plasma membrane H+-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum

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