Isolation and structural elucidation of pyridoxatin, a free radical scavenger of microbial origin.
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Biomedical subjects
Publications and source records attributed to H Seto.
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A 54-year-old woman with cerebellar metastasis from ovarian adenocarcinoma was reported. Two years before admission, she underwent 7 courses of CAP therapy (cisplatin, adriamycin, cyclophosphamide) for ovarian cancer. On admission, no extracranial tumor was noticed. After the removal of a cerebellar tumor, she was treated by combination chemotherapy with cisplatin and etoposide. Her serum level of CA-125, which was still high after surgery, decreased to the normal level following chemotherapy. Chemotherapy was repeated six times, and no recurrence was noticed 1 year after surgery. Combination chemotherapy with cisplatin and etoposide was considered effective in the treatment of intracranial metastasis from ovarian cancer.
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Attempts were made to elucidate the structure of the toxin isolated from the bile of carp Cyprinus carpio, which is possibly responsible for carp poisoning. By fast atom bombardment (FAB) mass spectrometry, along with 1H- and 13C-NMR, a molecular formula of C27H48O8S containing a sulfate ester group was deduced. Those and other analytical data allowed us to conclude the structure of carp toxin to be 5 alpha-cholestane-3 alpha, 7 alpha, 12 alpha, 26, 27-pentol 26-sulfate, which agreed essentially with that of 5 alpha-cyprinol, an alcohol specific to carp bile, in which the sulfate ester at the C-26 position is lacking.
This is the second reported case of a malignant fibrous histiocytoma of the heart that metastasized to the brain. A 33-year-old woman developed headache, nausea, and ataxic gait 9 months after removal of the tumor from the left atrium of the heart. Computed tomographic and magnetic resonance imaging scans disclosed multiple metastatic tumors in the brain. Although dramatic improvement in her symptoms and signs followed the removal of the brain tumors, she died of tumor recurrence in the left atrium 3 months after the removal of the metastatic brain tumors.
A rare case of suprasellar pituitary adenoma arising from the pars tuberalis in a 53-year-old woman is presented. The tumor was located exclusively above the diaphragma sellae, and no invasion into the sella turcica was noted.
An enzyme catalyzing the formation of an unusual C-P bond that is involved in the biosynthesis of the antibiotic bialaphos (BA) was isolated from the cell extract of a mutant (NP71) of Streptomyces hygroscopicus SF1293. This enzyme, carboxyphosphonoenolpyruvate (CPEP) phosphonomutase, was first identified as a protein lacking in a mutant (NP213) defective in one of the steps in the pathway to BA. The first 30 residues of the amino terminus of this protein were identical to those predicted by the nucleotide sequence of the gene that restored BA production to NP213. The substrate of the enzyme, a P-carboxylated derivative of phosphoenolpyruvate named CPEP, was also isolated from the broth filtrate of NP213 as a new biosynthetic intermediate of BA. CPEP phosphonomutase catalyzes the rearrangement of the carboxyphosphono group of CPEP to form the C-P bond of phosphinopyruvate.
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Variapeptin and citropeptin were found as novel hexadepsipeptide antibiotics produced by Streptomyces variabilis and Streptomyces flavidovirens, respectively. Their structures were elucidated by NMR spectral analysis including a variety of 2D techniques. Variapeptin and citropeptin are structurally realted to azinothricin and A83586C, respectively.
We cloned six different DNA fragments from a curromycin producing strain, Streptomyces hygroscopicus 358AV2, which confer curromycin-resistance on a curromycin non-producing and sensitive strain, S. hygroscopicus Rgll, a protoplast regenerant of the strain 358AV2. We studied the plasmid pSHR2 carrying one of the DNA fragments. By Southern blot analysis, the cloned DNA sequence in pSHR2 was found to be deleted in the Rgll genome. From the Rgll strain, a curromycin producing revertant A-4 was obtained, indicating that the structural genes for the curromycin biosynthesis and resistance are retained in the Rgll genome. Based on the existence of A-4 and the deletion of the DNA region corresponding to the cloned DNA sequence in the Rgll genome, we conclude that the cloned DNA sequence carries a regulatory gene governing curromycin-resistance but not the resistance gene itself. The smallest DNA region in pSHR2 conferring curromycin-resistance was sequenced, and it was found that there were two small open reading frames (ORF) on each strand of the cloned DNA. In-frame fusion of ORFs to the reporter gene lacZ revealed that one ORF designated cre was indeed translated in vivo. The putative gene product deduced from the cre ORF is a basic and hydrophilic protein having a calculated molecular weight of 6 kdaltons.
To study the relationship between citrate synthase and 2-phosphinomethylmalic acid (PMM) synthase, which catalyzes a very similar reaction comparable to citrate formation in the biosynthesis of a herbicide, bialaphos, citrate synthase was purified from the mycelium of Streptomyces hygroscopicus SF-1293, a bialaphos-producing organism. The overall purification was 440-fold with a yield of 4.4% from cell-free extract. Based on comparison with PMM synthase, it has been concluded that citrate synthase of S. hygroscopicus is quite different from PMM synthase in several aspects such as enzymatic properties, amino acid composition. N-terminal amino acid sequence, and stereo-chemical reaction mechanism.
A culture similar to Streptomyces variabilis was found to produce a novel cyclic hexadepsipeptide antibiotic named variapeptin. Variapeptin is structurally related to azinothricin, A83586C, and citropeptin. The antibiotic was active against Gram-positive bacteria and showed cytotoxic activity against mammalian cells.
An actinomycete identified as Streptomyces flavidovirens was found to produce a new cyclic hexadepsipeptide antibiotic, designated citropeptin. Citropeptin showed antitumor activity against P388 murine leukemia.