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41.
Masakazu Miyakado Isamu Nakayama Hirosuke Yoshioka Nobuji Nakatani 《Bioscience, biotechnology, and biochemistry》2013,77(7):1609-1611
It was evidenced that mutagenic principles in tryptophan pyrolysate, 3-amino-1,4-dimethyl-5H pyrido(4,3-b) indole and 3-amino-1-methyl-5H pyrido(4,3-b) indole (abbreviated as Trp-P-1 and Trp-P-2, respectively) bind to DNA without activation by rat liver microsomes. The bindings of Trp-P-1 and Trp-P-2 were not random and did not introduce strand scissions into DNA. Trp-P-1 bound more easily than Trp-P-2. The bindings of these mutagenic principles to DNA were concluded by using negatively superhelical simian virus 40 (SV40) DNA from following experimental data. (1) The intensity of ethidium bromide (EtBr)-DNA fluorescence by illumination with UV light and the electrophoretic mobility of superhelical DNA in agarose gel decreased as a function of the amounts of Trp-P-1 and Trp-P-2. (2) In vitro RNA synthesis catalyzed by Escherichia coli DNA-dependent RNA polymerase and nick-translation catalyzed by Escherichia coli DNA polymerase I (Kornberg enzyme) were inhibited significantly on DNA treated with Trp-P-1 and Trp-P-2. (3) The negative superhelicity of SV40 DNA introduces unpaired regions into DNA. These regions can be cleaved by single-strand-specific S1 endonuclease to generate unit length linear duplex molecules. It was found that this S1-sensitivity of DNA decreased by treatment with Trp-P-1. (4) The cleavage patterns of Trp-P-1 treated DNA with five restriction endonucleases were investigated. The protection of the cleavage site by the drug was observed against HincII, HindIII and EcoRII, whereas not against HaeIII and HinfI. These results show that the binding of Trp-P-1 to DNA is not random. Identical results were also obtained in Trp-P-2.However, the bindings of Trp-P-1 and Trp-P-2 were not so tight, and phenol extraction of the complex dissociated these drugs from DNA. 相似文献
42.
The presence of α-ketoglutarate (α-KG) dehydrogenase complex in the glutamate-producing bacteria was demonstrated for the first time with Brevibacterium flavum. The partially purified enzyme, which was specific to KG and NAD+ with the usual requirements for other co-factors, was labile and stabilized by glycerol, Mg2+, and thiamine pyrophosphate. The enzyme showed an optimum pH of 7.6 and Kms of 80, 86, and 61 μm for KG, NAD+, and CoA, respectively, cis-Aconitate, succinyl-CoA, NADPH, NADH, pyruvate, and oxalacetate strongly inhibited the activity, while it was activated by acetyl-CoA, but not by AMP. Various inorganic and organic salts also inhibited the activity. When cells were cultured in glucose and acetate media, the specific activity of the cell extracts increased markedly and reached to a maximum at the late-logarithmic phase. Then, it decreased to the basal level. The addition of glutamate stimulated the synthesis of the enzyme. 相似文献
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Growth of Brevibacterium flavum FA-1-30 and FA-3-115, L-lysine producers derived from Br. flavum No. 2247 as S-(2-aminoethyl)-L-cysteine (AEC) resistant mutants, was inhibited by α-amino-β-hydroxyvaleric acid (AHV), and this inhibition was reversed by L-threonine. All the tested AHV resistant mutants derived from FA-1-30 accumulated more than 4 g/liter of L-threonine in media containing 10% glucose, and the best producer, FAB-44, selected on a medium containing 5 mg/ml of AHV produced about 15 g/liter of L-threonine. Many of AHV resistant mutants selected on a medium containing 2 mg/ml of AHV accumulated L-lysine as well as L-threonine, AHV resistant mutants derived from FA-3-115 produced 10.7 g/liter of L-threonine maximally. AEC resistant mutants derived from strains BB–82 and BB–69, which were L-threonine producers derived from Br. flavum No. 2247 as AHV resistant mutants, did not produce L-threonine more than the parental strains, and moreover, many of them did not accumulate L-threonine but L-lysine. Homoserine dehydrogenases of crude extracts from L-threonine producing AHV resistant mutants derived from FA–1–30 and FA–3–115 were insensitive to the inhibition by L-threonine, and those of L-threonine and L-lysine producing AHV resistant mutants from FA–1–30 were partially sensitive.Correlation between L-threonine or L-lysine production and regulations of enzymatic activities of the mutants was discussed. 相似文献
47.
Isamu Shiio Yasuhiko Toride Shin-Ichi Sugimoto 《Bioscience, biotechnology, and biochemistry》2013,77(12):3091-3098
Mutants with low pyruvate dehydrogenase (PD) activities were derived from a pyruvate kinase-deficient lysine-producing mutant of Brevibacterium flavum, No. 22. They were selected as prototrophic revertants of the acetate auxotrophs of strain No. 22. Among them strain KD-11 produced 55g/liter of lysine as its HCI salt when cultured for 72 hr in a medium containing lOOg/liter of glucose, soybean-meal hydrolysate and methionine. The lysine yield of strain KD-11 was the highest ever reported (55%). The mutant required a higher concentration of methionine for maximum production and gave a smaller amount of cell mass in cultivation than its parent. PD activity of strain No. 22 was stimulated by cysteine, stabilized by glycerol, and gave apparent Kms of 89, 22, 380, 83 μM for pyruvate, coenzyme A, 3-acetylpyridine adenine dinucleotide, and NAD, respectively, under standard conditions. The apparent Km for NAD of PD from strain KD-11 was 10-times higher than that from No. 22. When the concentration of NAD was low, the cell extracts of strain KD-11 showed low PD activity. The specific activity of phosphoenolpyruvate carboxylase of strain KD-11 was slightly higher than that of strain No. 22, while the inhibition by aspartate of the former enzyme was weaker than that of the latter. 相似文献
48.
Blasticidin S deaminase (EC 3.5.4.23) was purified by affinity chromatography using a column of Sepharose 4B coupled with pyrimidinoblasticidin S as a ligand. The Michaelis constant Km and the maximum velocity Fmax varied with pH, which suggests that enzyme ionization is important either for substrate binding or for catalytic activity. The inflection point at pH 8.6 ~ 8.9 in the plot of pKm versus pH was attributed to an enzyme amino group which corresponded to the carboxyl group of substrates, and an inflection at pH 5.3 in the log Vmax-pH plot was assigned to the imidazole group of histidine, which appeared to be critical for catalytic deaminohydroxylation. The binding of substrates by the enzyme was inferred to be promoted thermodynamically, and activation of the substrate-enzyme complex was presumed to proceed endothermically. From the results obtained, a hypothetical mode of reaction for blasticidin S deaminase is proposed. 相似文献
49.
Strain MR-12 which was derived from Candida cloacae M-l as a mutant unable to assimilate n-alkane showed marked increase in dicarboxylic acid (DC) productivity from n-alkane.Resting cells of strain MR-12 produced 42.7g/liter of n-tetradecane 1,14-dicarboxylic acid (DC-16) from n-hexadecane (n-C16) after 72 hr’ incubation. DC degradation activities of strain M-1 and MR-12 were found to be markedly reduced and their activities against DC-16 decreased to 40% and 10% of that of the parent strain, respectively.Strain M-1 and MR-12 produced DC from the various oxidized derivatives of n-alkane such as alcohol, diol, aldehyde, fatty acid and methyl- or ethylester of fatty acid other than n-alkane.The carbon balance in n-C16 oxidation was determined by using resting cells of strain MR-12 and about 60% of utilized carbon was recovered as DC-16 and about 40% was recovered as CO2. 相似文献
50.
Jiannong Li Keiryn Bennett Alexey Stukalov Bin Fang Guolin Zhang Takeshi Yoshida Isamu Okamoto Jae‐Young Kim Lanxi Song Yun Bai Xiaoning Qian Bhupendra Rawal Michael Schell Florian Grebien Georg Winter Uwe Rix Steven Eschrich Jacques Colinge John Koomen Giulio Superti‐Furga Eric B Haura 《Molecular systems biology》2013,9(1)
We hypothesized that elucidating the interactome of epidermal growth factor receptor (EGFR) forms that are mutated in lung cancer, via global analysis of protein–protein interactions, phosphorylation, and systematically perturbing the ensuing network nodes, should offer a new, more systems‐level perspective of the molecular etiology. Here, we describe an EGFR interactome of 263 proteins and offer a 14‐protein core network critical to the viability of multiple EGFR‐mutated lung cancer cells. Cells with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) had differential dependence of the core network proteins based on the underlying molecular mechanisms of resistance. Of the 14 proteins, 9 are shown to be specifically associated with survival of EGFR‐mutated lung cancer cell lines. This included EGFR, GRB2, MK12, SHC1, ARAF, CD11B, ARHG5, GLU2B, and CD11A. With the use of a drug network associated with the core network proteins, we identified two compounds, midostaurin and lestaurtinib, that could overcome drug resistance through direct EGFR inhibition when combined with erlotinib. Our results, enabled by interactome mapping, suggest new targets and combination therapies that could circumvent EGFR TKI resistance. 相似文献