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1.
L. Escalante I. Ramos I. Imriskova E. Langley S. Sanchez 《Applied microbiology and biotechnology》1999,52(4):572-578
The effect of glucose on growth and anthracycline production by Streptomyces peucetius var. caesius was examined in a chemically defined medium. Glucose concentrations above 100 mM inhibited anthracycline synthesis in the
original strain without causing significant change in growth and final pH values. This effect was observed when the carbohydrate
was added initially or after 24 h fermentation, but not when added during the stationary growth phase. When the microorganism
was pregrown in 100 mM glucose and then transferred to a resting cell system with 444 mM glucose, no significant differences
in antibiotic production were observed compared to the control without glucose. The negative effect of glucose on antibiotic
synthesis was not observed in a mutant (2-dogR–21) resistant to growth inhibition by 2-deoxyglucose. Glucose consumption by this mutant was approximately 30% of that utilized
by the original strain. Compared to the original strain, the mutant 2-dogR–21 exhibited a reduction of 50% in glucose transport and an 85% decrease in glucose kinase activity. The experimental evidence
obtained suggests that glucose represses anthracycline formation in a transitory manner and that this effect is related to
glucose transport and phosphorylation.
Received: 15 January 1999 / Received revision: 7 April 1999 / Accepted: 1 May 1999 相似文献
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3.
Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius 总被引:10,自引:0,他引:10
F Arcamone G Cassinelli G Fantini A Grein P Orezzi C Pol C Spalla 《Biotechnology and bioengineering》1969,11(6):1101-1110
Streptomyces peucetius var. caesius, obtained from S. peucetius, the daunomycin producing microorganism, by mutagenic treatment, differs from the parent culture by the color of the vegetative and aerial mycelia and by its antibiotic, producing ability. S. peucetius var. caesius accumulates adriamycin in submerged and aerated culture on a medium containing glucose, brewer's yeast, and inorganic, salts both in shake flasks and in stirred fementers. Isolation of the product is performed by solvent extraction, chromatography on buffered cellulose columns, and crystallization as the hydrochloride. The new antitumor agent, adriamycin, is the 14-hydroxv derivative of daunomyein. 相似文献
4.
Beatriz Ruiz-Villafán Romina Rodríguez-Sanoja Guillermo Aguilar-Osorio Guillermo Gosset Sergio Sanchez 《Applied microbiology and biotechnology》2014,98(13):6061-6071
Glucose kinases (Glks) are enzymes of the glycolytic pathway involved in glucose phosphorylation. These enzymes can use various phosphoryl donors such as ATP, ADP, and polyphosphate. In several streptomycetes, ATP-glucose kinase (ATP-Glk) has been widely studied and regarded as the main glucose phosphorylating enzyme and is likely a regulatory protein in carbon catabolite repression. In cell extracts from the doxorubicin overproducing strain Streptomyces peucetius var. caesius, grown in glucose, a polyphosphate-dependent Glk (Pp-Glk) was detected by zymogram. Maximum activity was observed during the stationary growth phase (48 h) of cells grown in 100 mM glucose. No activity was detected when 20 mM glutamate was used as the only carbon source, supporting a role for glucose in inducing this enzyme. Contrary to wild-type strains of Streptomyces coelicolor, Streptomyces lividans, and Streptomyces thermocarboxydus K-155, S. peucetius var. caesius produced 1.8 times more Pp-Glk than ATP-Glk. In addition, this microorganism produced five and four times more Pp-Glk and anthracyclines, respectively, than its wild-type S. peucetius parent strain, supporting a role for this enzyme in antibiotic production in the overproducer strain. A cloned 726-bp DNA fragment from S. peucetius var. caesius encoded a putative Pp-Glk, with amino acid identities between 83 and 87 % to orthologous sequences from the above-cited streptomycetes. The cloned fragment showed the polyphosphate-binding sequences GXDIGGXXIK, TXGTGIGSA, and KEX(4)SWXXWA. Sequences for the Zn-binding motif were not detected in this fragment, suggesting that Pp-Glk is not related to the Glk ROK family of proteins. 相似文献
5.
D. Segura C. Santana R. Gosh L. Escalante S. Sanchez 《Applied microbiology and biotechnology》1997,48(5):615-620
In Streptomyces peucetius var. caesius, the production of anthracyclines was suppressed either by 330 mM d-glucose or 25 mM phosphate. In addition, the anthracycline doxorubicin and the glucose analogue 2-deoxyglucose inhibited
the growth of this microorganism at concentrations of 0.025 mM and 10 mM respectively. Spontaneous and induced mutants, resistant
to the action of these compounds, were isolated, tested and chosen by their ability to overproduce anthracyclines. Genetic
recombination between representative mutants was carried out by the protoplast fusion technique. Some recombinants carrying
resistance to doxorubicin, phosphate and 2-deoxyglucose produced more than 40-fold greater levels of anthracyclines than those
obtained with the parental strain. This improvement resulted in total antibiotic titres of more than 2 g/l culture medium
at 6 days of fermentation.
Received: 14 April 1997 / Received revision: 19 June 1997 / Accepted: 4 July 1997 相似文献
6.
Semisynthetic derivatives of daunomycinone with 7,9-isopropylacetal, 7-O-methyl, 7-O-(4-penten-2-yl), and 7-O-(2-hydroxyethyl)
substituents were converted byStreptomyces peucetius var.caesius (an adriamycin-blocked mutant) into 7-deoxy-13-dihydrodaunomycinone, while daunomycinone was transformed into 13-dihydrodaunomycinone
(predominantly) and 7-deoxy-13-dihydrodaunomycinone.S. coeruleorubidus mutants 24–74 (accumulating aclavinone derivatives instead of daunomycin and related compounds) and 96-85 (producing no anthracycline
substances), andS. aureofaciens B-96 (a tetracycline-blocked mutant) transformed the above substrates into the corresponding 13-dihydro derivatives, with
the exception of 7,9-isopropylacetal daunomycinone which remained intact. 7-O-Propyn-1-yl daunomycinone was not transformed
by any of the strains used under the conditions. 相似文献
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8.
A 13C-NMR study of the biosynthesis of daunomycin adriamycin from propionate[1-13C] has been carried out in cultures of Streptomyces peucetius var. caesius. Results give direct support for the postulate that a propionate ‘starter’ is involved in the biosynthesis of both metabolites. 相似文献
9.
D. O. Klymyshin O. Ya. Nimets O. M. Stefanyshyn V. O. Fedorenko 《Cytology and Genetics》2013,47(4):197-201
Strains of the actinomycetes Streptomyces nogalater Lv65, S. echinatus DSM40730, and S. peucetius subsp. caesius ATCC27952 are producers of the anthracycline antibiotics nogalamycin, aranciamycin, and doxorubicin, respectively. This work was focused on the impact produced by the expression of the regulatory lndYR and wblA gh genes on the secondary metabolism and morphogenesis of these bacteria. Introducing regulators into the composition of replicative plasmids in the streptomycetes in question leads to a decrease in the synthesis of anthracyclines, whereas the expression of lndYR in cells of S. peucetius subsp. caesius ATCC27952 suppresses the sporulation of the doxorubicin producer which may indicate the presence of their homologues in the genomes. The identification of these genes for the purpose of their further directed inactivation may be a successful tool for obtaining strains with an increased level of synthesis of clinically important compounds, as well as it can allow us to establish particular stages in the regulation of the secondary metabolism of anthracycline antibiotics. 相似文献
10.
Kiviharju K Leisola M Eerikäinen T 《Journal of industrial microbiology & biotechnology》2004,31(10):475-481
Streptomyces peucetius var. caesius is an aerobic bacterium that produces doxorubicin as a secondary metabolite. A mixture design was applied for the screening of suitable complex medium components in the cultivation of S. peucetius var. caesius N47, which is an -rhodomycinone-accumulating mutant strain. -Rhodomycinone is a non-glycosylated precursor of doxorubicin. Best growth results were obtained with soy peptone and beef extract. A central composite face-centered (CCF) experimental design was constructed for the investigation of pH, temperature and dissolved oxygen (DO) effects on the cultivation growth phase. Another CCF was applied to the production phase to investigate the effects of aeration, pH, temperature and stirring rate on -rhodomycinone production. An increase in cultivation temperature increased both cell growth and glucose consumption rate. Best -rhodomycinone productivities were obtained in temperatures around 30°C. DO control increased all growth phase responses, but aeration in the production phase coupled with pH decrease resulted in rapid -rhodomycinone decay in the medium. In non-aerated production phases a pH change resulted in better productivity than in experiments without pH change. A pH increase with a temperature decrease seemed most beneficial for productivity. This implies that dynamic control strategies in batch production of -rhodomycinone could increase the overall process productivity. 相似文献
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Xiaoru Wang Xiaorong Tian Yuanjie Wu Xiaofang Shen Songbai Yang 《Preparative biochemistry & biotechnology》2013,43(6):514-521
AbstractDoxorubicin (DXR), which is produced by Streptomyces peucetius, is an important anthracycline-type antibiotic used for the treatment of various cancers. However, due to the low DXR productivity of wild-type S. peucetius, it is difficult to produce DXR by one-step fermentation. In this study, a DXR-resistance screening method was developed to screen for DXR high-producing mutants. Then, S. peucetius SIPI-11 was treated several times with UV and ARTP (atmospheric and room temperature plasma) to induce mutations. Treated strains were screened by spreading on a DXR-containing plate, isolating a mutant (S. peucetius 33-24) with enhanced DXR yield (570?mg/L vs. 119?mg/L for the original strain). The components of the fermentation medium, including the carbon and nitrogen sources, were optimized to further enhance DXR yield (to 850?mg/L). The pH of the fermentation medium and culture temperature were also optimized for effective DXR production. Finally, DXR production by S. peucetius 33-24 was investigated in flask culture and a fermenter. The yield of DXR was as high as 1100?mg/L in a 5-L fermenter, which is the highest DXR productivity reported thus far, suggesting that S. peucetius 33-24 has the potential to produce DXR by direct fermentation. 相似文献
13.
Intergeneric Conjugation in Streptomyces peucetius and Streptomyces sp. Strain C5: Chromosomal Integration and Expression of Recombinant Plasmids Carrying the chiC Gene 总被引:1,自引:0,他引:1 下载免费PDF全文
Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to Streptomyces circumvents problems such as host-controlled restriction and instability of foreign DNA during the transformation of Streptomyces protoplasts. The anthracycline antibiotic-producing strains Streptomyces peucetius and Streptomyces sp. strain C5 were transformed using E. coli ET12567(pUZ8002) as a conjugal donor. When this donor species, carrying pSET152, was mated with Streptomyces strains, the resident plasmid was mobilized to the recipient and the transferred DNA was also integrated into the recipient chromosome. Analysis of the exconjugants showed stable integration of the plasmid at a single chromosomal site (attB) of the Streptomyces genome. The DNA sequence of the chromosomal integration site was determined and shown to be conserved. However, the core sequence, where the crossover presumably occurred in C5 and S. peucetius, is TTC. These results also showed that the C31 integrative recombination is active and the phage attP site is functional in S. peucetius as well as in C5. The efficiency and specificity of C31-mediated site-specific integration of the plasmid in the presence of a 3.7-kb homologous DNA sequence indicates that integrative recombination is preferred under these conditions. The integration of plasmid DNA did not affect antibiotic biosynthesis or biosynthesis of essential amino acids. Integration of a single copy of a mutant chiC into the wild-type S. peucetius chromosome led to the production of 30-fold more chitinase. 相似文献
14.
Summary The nodulatingRhizobium trifolii strain 24 and its non-nodulating mutant 24 nod–3 have been examined. The exopolysaccharides of both cultures studied contained mannose, galactose and glucose at similar molar ratios. On the other hand some quantitative differences have been found between the lipopolysaccharides in respect of the composition of neutral sugars. Glucose and rhamnose were the main constituents of the nodulating strain 24, whereas rhamnose and galactose in non-nodulating mutant 24 nod–3 deprived of the plasmid pWZ2. 相似文献
15.
Isolation and characterization of stable mutants ofStreptomyces peucetius defective in daunorubicin biosynthesis 总被引:1,自引:0,他引:1
Daunorubicin and its derivative doxorubicin are antitumour anthracycline antibiotics produced byStreptomyces peucetius. In this study we report isolation of stable mutants ofS. peucetius blocked in different steps of the daunorubicin biosynthesis pathway. Mutants were screened on the basis of colony colour
since producer strains are distinctively coloured on agar plates. Different mutants showed accumulation of aklaviketone, ε-rhodomycinone,
maggiemycin or 13-dihydrocarminomycin in their culture filtrates. These results indicate that the mutations in these isolates
affect steps catalysed bydnrE (mutants SPAK and SPMAG),dnrS (SPFS and SPRHO) anddoxA (SPDHC) gene products. 相似文献
16.
V. Hernández-Montalvo F. Valle F. Bolivar G. Gosset 《Applied microbiology and biotechnology》2001,57(1-2):186-191
Due to catabolite repression in microorganisms, sugar mixtures cannot be metabolized in a rapid and efficient manner. Therefore, the development of mutant strains that avoid this regulatory system is of special interest to fermentation processes. In the present study, the utilization of sugar mixtures by an Escherichia coli mutant strain devoid of the phosphotransferase system (PTS) was characterized. This mutant can transport glucose (PTS- Glucose+ phenotype) by a non-PTS mechanism as rapidly as its wild-type parental strain. In cultures grown in minimal medium supplemented with glucose-xylose or glucose-arabinose mixtures, glucose repressed arabinose- or xylose-utilization in the wild-type strain. However, under the same culture conditions with the PTS- Glucose+ mutant, glucose and arabinose were co-metabolized, but glucose still exerted a partial repressive effect on xylose consumption. In cultures growing with a triple mixture of glucose-arabinose-xylose, the wild-type strain sequentially utilized glucose, arabinose and finally, xylose. In contrast, the PTS- Glucose+ strain co-metabolized glucose and arabinose, whereas xylose was utilized after glucose-arabinose depletion. As a result of glucose-arabinose co-metabolism, the PTS- Glucose+ strain consumed the total amount of sugars contained in the culture medium 16% faster than the wild-type strain. [14C]-Xylose uptake experiments showed that in the PTS- Glucose+ strain, galactose permease increases xylose transport capacity and the observed partial repression of xylose utilization depends on the presence of intracellular glucose. 相似文献
17.
Kiviharju K Moilanen U Leisola M Eerikäinen T 《Applied microbiology and biotechnology》2007,73(6):1267-1274
The behavior of Streptomyces peucetius var. caesius N47 was studied in a glucose limited chemostat with a complex cultivation medium. The steady-state study yielded the characteristic
constants μ
max over 0.10 h−1, Y
XS 0.536 g g−1, and mS 0.54 mg g−1 h−1. The product of secondary metabolism, ɛ-rhodomycinone, was produced with characteristics Y
PX 12.99 mg g−1 and m
P 1.20 mg g−1 h−1. Significant correlations were found for phosphate and glucose consumption with biomass and ɛ-rhodomycinone production. Metabolic
flux analysis was conducted to estimate intracellular fluxes at different dilution rates. TCA, PPP, and shikimate pathway
fluxes exhibited bigger values with production than with growth. Environmental perturbation experiments with temperature,
airflow, and pH changes on a steady-state chemostat implied that an elevation of pH could be the most effective way to shift
the cells from growing to producing, as the pH change induced the biggest transient increase to the calculated ɛ-rhodomycinone
flux. 相似文献
18.
Studies on the production of daunomycinonederived glycosides and related metabolites inStreptomyces coeruleorubidus andStreptomyces peucetius 总被引:1,自引:1,他引:0
Strains ofStreptomyces coeruleorubiduě ISP 5145,JA 10092 and 39–146, differing mutually in antibiotic activity, were found to produce identical spectrum of metabolites (at
least nine antibiotically active glycosides, 13-dihydrodaunomycinone, ε-rhodomycinone and a larger number of unidentified
compounds); only trace quantities of daunomycin and daunomycinone could be detected. A fraction of glycosides with a higher
Rf (0.4–0.7), isolated from strain 39–146, could be transformed to daunomycin by mild hydrolysis and to daunomycinone by total
hydrolysis.Streptomyces peucetius IMI 101 335 differed fromStreptomyces coeruleorubidus in an increased production of ε-rhodomycinone and a lower content of glycosides; the zone of daunomycin was most pronounced
among the glycoside spots.Streptomyces coeruleorubidus 39-146 exhibited the highest activity in a medium containing 3.5% soluble starch, 3.0% soybean meal, 0.3% NaCl and 0.3% CaCo3; glucose was a more useful carbon source for the remaining strains The activity ofStreptomyces coeruleorubidus was inhibited by 1-propanol, Na-propionate,5,5-diethylbarbiturate and bacitracin. Ferrous sulphate stimulated the production of glycosides only in strain JA 10092, decreasing
simultaneously the production of aglycones. 相似文献
19.
《Critical reviews in biotechnology》2013,33(1):22-48
Lignocellulosic biomass from agricultural and agro-industrial residues represents one of the most important renewable resources that can be utilized for the biological production of ethanol. The yeast Saccharomyces cerevisiae is widely used for the commercial production of bioethanol from sucrose or starch-derived glucose. While glucose and other hexose sugars like galactose and mannose can be fermented to ethanol by S. cerevisiae, the major pentose sugars D-xylose and L-arabinose remain unutilized. Nevertheless, D-xylulose, the keto isomer of xylose, can be fermented slowly by the yeast and thus, the incorporation of functional routes for the conversion of xylose and arabinose to xylulose or xylulose-5-phosphate in Saccharomyces cerevisiae can help to improve the ethanol productivity and make the fermentation process more cost-effective. Other crucial bottlenecks in pentose fermentation include low activity of the pentose phosphate pathway enzymes and competitive inhibition of xylose and arabinose transport into the cell cytoplasm by glucose and other hexose sugars. Along with a brief introduction of the pretreatment of lignocellulose and detoxification of the hydrolysate, this review provides an updated overview of (a) the key steps involved in the uptake and metabolism of the hexose sugars: glucose, galactose, and mannose, together with the pentose sugars: xylose and arabinose, (b) various factors that play a major role in the efficient fermentation of pentose sugars along with hexose sugars, and (c) the approaches used to overcome the metabolic constraints in the production of bioethanol from lignocellulose-derived sugars by developing recombinant S. cerevisiae strains. 相似文献
20.
Gustavo Graciano Fonseca Nuno Miguel Barbosa de Carvalho Andreas Karoly Gombert 《Applied microbiology and biotechnology》2013,97(11):5055-5067
The yeast Kluyveromyces marxianus has been pointed out as a promising microorganism for a variety of industrial bioprocesses. Although genetic tools have been developed for this yeast and different potential applications have been investigated, quantitative physiological studies have rarely been reported. Here, we report and discuss the growth, substrate consumption, metabolite formation, and respiratory parameters of K. marxianus CBS 6556 during aerobic batch bioreactor cultivations, using a defined medium with different sugars as sole carbon and energy source, at 30 and 37 °C. Cultivations were carried out both on single sugars and on binary sugar mixtures. Carbon balances closed within 95 to 101 % in all experiments. Biomass and CO2 were the main products of cell metabolism, whereas by-products were always present in very low proportion (<3 % of the carbon consumed), as long as full aerobiosis was guaranteed. On all sugars tested as sole carbon and energy source (glucose, fructose, sucrose, lactose, and galactose), the maximum specific growth rate remained between 0.39 and 0.49 h?1, except for galactose at 37 °C, which only supported growth at 0.31 h?1. Different growth behaviors were observed on the binary sugar mixtures investigated (glucose and lactose, glucose and galactose, lactose and galactose, glucose and fructose, galactose and fructose, fructose and lactose), and the observations were in agreement with previously published data on the sugar transport systems in K. marxianus. We conclude that K. marxianus CBS 6556 does not present any special nutritional requirements; grows well in the range of 30 to 37 °C on different sugars; is capable of growing on sugar mixtures in a shorter period of time than Saccharomyces cerevisiae, which is interesting from an industrial point of view; and deviates tiny amounts of carbon towards metabolite formation, as long as full aerobiosis is maintained. 相似文献