<i>Acremonium chrysogenum</i> differentiation and biosynthesis of cephalosporin

Bartoshevich, Yu. E.; Zaslavskaya, P. L.; Novak, Mark J.; Yudina, O. D.

doi:10.1002/jobm.3620300503

Cited by 45 publications

(40 citation statements)

References 8 publications

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“…For our microscopic investigations, fungal morphology was monitored after 48, 72, 96, and 120 h of growth in liquid medium, using the five different strains described above. Arthrospore formation in the A3/2 strain starts at 96 h and is correlated with an increase in the yield of cephalosporin C biosynthesis (1,30). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

A Homologue of the Aspergillus velvet Gene Regulates both Cephalosporin C Biosynthesis and Hyphal Fragmentation in Acremonium chrysogenum

Dreyer

Eichhorn²,

Friedlin³

et al. 2007

Appl Environ Microbiol

127

102

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The Aspergillus nidulans velvet (veA) gene encodes a global regulator of gene expression controlling sexual development as well as secondary metabolism. We have identified the veA homologue AcveA from Acremonium chrysogenum, the major producer of the ␤-lactam antibiotic cephalosporin C. Two different disruption strains as well as the corresponding complements were generated as a prelude to detailed functional analysis. Northern hybridization and quantitative real-time PCR clearly indicate that the nucleus-localized AcVEA polypeptide controls the transcriptional expression of six cephalosporin C biosynthesis genes. The most drastic reduction in expression is seen for cefEF, encoding the deacetoxycephalosporine/deacetylcephalosporine synthetase. After 120 h of growth, the cefEF transcript level is below 15% in both disruption strains compared to the wild type. These transcriptional expression data are consistent with results from a comparative and time-dependent high-performance liquid chromatography analysis of cephalosporin C production. Compared to the recipient, both disruption strains have a cephalosporin C titer that is reduced by 80%. In addition to its role in cephalosporin C biosynthesis, AcveA is involved in the developmentally dependent hyphal fragmentation. In both disruption strains, hyphal fragmentation is already observed after 48 h of growth, whereas in the recipient strain, arthrospores are not even detected before 96 h of growth. Finally, the two mutant strains show hyperbranching of hyphal tips on osmotically nonstabilized media. Our findings will be significant for biotechnical processes that require a defined stage of cellular differentiation for optimal production of secondary metabolites.

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Section: Resultsmentioning

confidence: 99%

A Homologue of the Aspergillus velvet Gene Regulates both Cephalosporin C Biosynthesis and Hyphal Fragmentation in Acremonium chrysogenum

Dreyer

Eichhorn²,

Friedlin³

et al. 2007

Appl Environ Microbiol

127

102

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“…Particular situations of nutrient and oxygen concentrations in a pellet might create a physiological context encouraging a structural differentiation of the idiophasic hypha of the fungus. Fragmentation of idiophasic fungal hyphae is under metabolic and environmental control (Gow, 1994) and may result in differentiated cell structures having particular metabolic properties: for example yeast-like cells synthesizing the antibiotic cephalosporin in Acremonium chrysogenum (Bartoshevich et al, 1990;Sandor et al, 1998). In the case of P. chrysosporium it has been reported that a hyperoxidant state of growth, caused by limiting respirable carbon, induces a disorganization in the intracellular architecture of LiP-secreting hyphae in mycelial pellets, which in turn may promote enzyme production (Zacchi et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

In situ localization of manganese peroxidase production in mycelial pellets of Phanerochaete chrysosporium

Jimenez-Tobon

Kurzątkowski²,

Rozbicka³

et al. 2003

Microbiology

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The ultrastructure of Phanerochaete chrysosporium hyphae from pellets in submerged liquid cultures was investigated in order to learn more about the interrelation between fungal architecture and manganese peroxidase (MnP) production. At day 2 of cultivation, some subapical regions of hyphae in the outer and middle zones of the pellet initiated differentiation into intercalary thick-walled chlamydospore-like cells of about 10 mm diameter. At the periphery of the cytoplasm of these cells, a large number of mitochondria and Golgi-like vesicles were observed. The sites of MnP production were localized at different stages of cultivation by an immunolabelling procedure. The immunomarker of MnP was mainly concentrated in the chlamydospore-like cells and principally distributed in Golgi-like vesicles located at the periphery of the cytoplasm. The apices of hyphae in the outer layer of the pellets were apparently minor sites of MnP production. Maximal MnP release into the culture supernatant coincided with apparent autolysis of the chlamydospore-like cells. Production of extracellular autolytic chitinase and protease coincided with the disappearance of these structures from the pellets. The chlamydospore-like cells observed in the mycelial pellets of P. chrysosporium could be metabolically active entities operating as an enzyme reservoir, delivering their content into the surrounding medium possibly by an enzyme-mediated autolytic process.

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“…This metabolite, if stable enough, would be an invaluable tool in the initiation of controlled gross autolysis of industrial-scale cultures, e.g., to facilitate the release of cell-bound or cell-absorbed metabolites [58], and in the stimulation of the conidiogenesis of weakly sporulating or nonsporulating industrial strains of filamentous fungi.…”

Section: Industrial Significancementioning

confidence: 99%

Regulation of Autolysis in Aspergillus nidulans

Emri

Molnár

Szilágyi

et al. 2008

Appl Biochem Biotechnol

115

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In terms of cell physiology, autolysis is the centerpiece of carbon-starving fungal cultures. In the filamentous fungus model organism Aspergillus nidulans, the last step of carbon-starvation-triggered autolysis was the degradation of the cell wall of empty hyphae, and this process was independent of concomitantly progressing cell death at the level of regulation. Autolysis-related proteinase and chitinase activities were induced via FluG signaling, which initiates sporulation and inhibits vegetative growth in surface cultures of A. nidulans. Extracellular hydrolase production was also subjected to carbon repression, which was only partly dependent on CreA, the main carbon catabolite repressor in this fungus. These data support the view that one of the main functions of autolysis is supplying nutrients for sporulation, when no other sources of nutrients are available. The divergent regulation of cell death and cell wall degradation provides the fungus with the option to keep dead hyphae intact to help surviving cells to absorb biomaterials from dead neighboring cells before these are released into the extracellular space. The industrial significance of these observations is also discussed in this paper.

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Acremonium chrysogenum differentiation and biosynthesis of cephalosporin

Cited by 45 publications

References 8 publications

A Homologue of the Aspergillus velvet Gene Regulates both Cephalosporin C Biosynthesis and Hyphal Fragmentation in Acremonium chrysogenum

A Homologue of the Aspergillus velvet Gene Regulates both Cephalosporin C Biosynthesis and Hyphal Fragmentation in Acremonium chrysogenum

In situ localization of manganese peroxidase production in mycelial pellets of Phanerochaete chrysosporium

Regulation of Autolysis in Aspergillus nidulans

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