New triene-ansamycins designated thiazinotrienomycins F (TT-F) and G (TT-G) and a new diene-ansamycin, benzoxazomycin, were isolated from a culture broth of Streptomyces sp. MJ672-m3 and their structures were elucidated by spectroscopic analyses. The Mean Graphs of TT-G suggests that the tumor growth inhibitory activities are almost as strong as TT-B, in respect of GI(50) and TGI against several human cancer cell lines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC), pholipeptin (1), was purified from the culture broth of Pseudomonas sp. by solvent extraction and column chromatography. Acid hydrolysis of 1 gave Leu, Ile, Ser, Thr, and Asp moieties. Although 1 was a peptide compound, fragmentation by mild hydrolysis was not accomplished under any conditions. So, we performed the structure elucidation using various 2D NMR techniques. In the NMR studies, the addition of a small amount of trifluoroacetic acid gave relatively sharp and resolved signals, such that the structure of this novel cyclic lipodepsipeptide consisting of 11 amino acids and a 3-hydroxydecanoic acid moiety could be determined. Chirality of the constituent amino acids was analyzed by chiral HPLC, but two Asp residues could not be distinguished because they were contained as a racemic mixture. Finally, their chiralities were determined by NMR analysis of (13)C-labeled 1 into which [L-(13)C]Asp had been biosynthetically incorporated.

The antibacterial activity of 2″-amino-2″-deoxyarbekacin (AmABK) and 2″-amino-5,2″-dideoxy-5-epiaminoarbekacin (Am2ABK) was comparable to, or slightly less than, that of arbekacin (ABK) against gram-positive and gram-negative bacteria, including 60 stock cultures and 50 clinical isolates ofPseudomonas aeruginosa, but more potent against 31 isolates of MRSA possessing an aminoglycoside-modifying enzyme APH(2″)/AAC(6'). AmABK and Am2ABK showed in vivo activity which paralleled in vitro MICs, and were less toxic than ABK in acute toxicity in mice and nephrotoxicity in rats. These results indicate that the 2″-amino group introduced to ABK confers high stabilization to the aminoglycoside-modifying enzymes, while reducing acute and renal toxicities.

The ansamycin antibiotic, herbimycin A, selectively inactivates cytoplasmic tyrosine kinases, most likely by binding irreversibly to the reactive SH group(s) of kinases. To further investigate the mechanism of herbimycin A action, we attempted to label tyrosine kinases with [ 14 C]herbimycin A. p60 v‐src and p2 10 BCR‐ABL in immune complexes were labeled with [ 14 C]herbimycin A, demonstrating that the antibiotic binds directly to tyrosine kinases. Digestion of [ 14 C]herbimycin A‐labeled p60 v‐src with Staphylococcus taureus V8 protease revealed that the herbimycin A binding site is within the C‐terminal 26‐kDa fragment of p60 v‐src , which contains the tyrosine kinase domain. Herbimycin A treatment inhibited labeling of p60 v‐src by [ 14 ]C]fluorosulfonylbenzoyl adenosine, an affinity labeling reagent of nucleotide binding sites, indicating that herbimycin A‐modified p60 v‐src cannot interact with ATP. The results suggest that herbimycin A inactivates tyrosine kinases by binding directly to the kinase domain, thereby inhibiting access to ATP.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A segment of the neocarzinostatin apoprotein gene corresponding to T30 to A91 of the protein was amplified using a polymerase chain reaction (PCR) with total DNA from Streptomyces carzinostaticus subsp. neocarzinostaticus E-793 (ATCC 15944) as the template and with 5'- and 3'-primers synthesized in consideration of the codon usage of streptomyces. The PCR product was cloned, sequenced and confirmed to direct an amino acid sequence reasonably well matching that reported. Using the PCR product as a probe, we cloned a DNA segment (2580 bp) spanning an open reading frame (ORF) for preapoprotein (leader peptide plus apoprotein) and its upstream and downstream flanking regions. The amino acid sequence deduced from the base sequence of the DNA clearly identified those amino acid residues which had remained inconsistent among different research groups. The base sequence homology with other apoprotein genes of related antibiotics was analyzed and was found to be limited within the structural gene.

The apoprotein gene for a chromoprotein antitumor antibiotic, C-1027, was cloned from the producer strain, Streptomyces globisporus C-1027, and sequenced. The process verified that; (1) the sequence included the entire structural gene directing a precursor of the apoprotein (pre-apoprotein having Met1---Ala33 leader peptide ahead of the apoprotein) and flanking regions, (2) the amino acid sequence of the apoprotein deduced from the base sequence perfectly matched the one based on protein analysis, (3) 3rd letters of the codons were 88% G or C, while the 1st plus the 2nd letters were 63% G or C, (4) the structural gene had 57% homology with that of macromomycin apoprotein (mcmA) while the flanking regions had little homology with the corresponding ones of mcmA, except some homology at the -10th and -35th promoter regions, and (5) the gene was transcribed as a monocistronic mRNA in an early growth phase, independent of chromophore production.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation and Structure Determination of Inostamycin, a Novel Inhibitor of Phosphatidylinositol TurnoverMasaya Imoto, Kazuo Umezawa, Yoshikazu Takahashi, Hiroshi Naganawa, Yoichi Iitaka, Hikaru Nakamura, Yumi Koizumi, Yumi Sasaki, Masa Hamada, Tsutomu Sawa, and Tomio TakeuchiCite this: J. Nat. Prod. 1990, 53, 4, 825–829Publication Date (Print):July 1, 1990Publication History Published online1 July 2004Published inissue 1 July 1990https://doi.org/10.1021/np50070a008RIGHTS & PERMISSIONSArticle Views214Altmetric-Citations34LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (272 KB) Get e-Alertsclose Get e-Alerts

This paper deals with a temperature field of a slightly heated two-dimensional jet injected normal to a cold cross flow. At the blowing rates of 0.2, 1.5 and 3.0 in two kinds of approaching boundary layer, the thermal mixing characteristics of the heated jet with the cross flow are experimentally clarified. The correlation between the temperature field and the complex flow one in the downstream region of the jet is made clear, in relation to the typical jet flow patterns. Comparison of the present results with the existing experimental data are represented.

A 1.6 kb Sph I-Sac I DNA fragment from Streptomyces macromomyceticus, expected to include the macromomycin (MCM) apoprotein gene, was sequenced. The fragment (1,556 bp) was found to include a putative promoter, an ORF directing pre-apoprotein which should be split into the leader peptide (Met1 to Gly32) and the MCM apoprotein (Ala33 to Ala144), and a putative terminator. The amino acid sequence deduced from the base sequence of the DNA is consistent with the amino acid sequence previously determined by the Edman degradation and other procedures applied to the protein, except base sequence AAC coding for Asn was found rather than Asp111 previously reported. The GC content of the 3rd letters throughout the ORF was 92% in contrast to the sum of the first and the second letters, 62%. There was a low GC content stretch of 20 bp (30% GC) at about 120 bp upstream of the ORF. The Pst I-Sph I 620 bp fragment including the low GC content stretch showed promoter activity when subcloned in a promoter probe vector. About 700 nucleotides long mRNA, which is long enough to span the ORF and the bordering regions, was identified using the Northern blot analysis. A primer extension experiment showed that the transcriptional starting point was A at 89 bp upstream of the ORF. Dot blot analysis of expression of MCM apoprotein gene indicated that the gene was expressed nearly constitutively, while production of holo MCM (the complex consisting of MCM apoprotein and a specific chromophore) depended greatly on culture conditions.

A mixed probe consisting of two synthetic deoxynucleotides (52 and 54 mers referred to as 50-mer) with arbitrarily chosen C or G for the third letters was prepared based on the amino acid sequences No. 31-48 and No. 72-90 of macromomycin (MCM) apoprotein and successfully used to clone the MCM apoprotein gene. Digestion with Sph I of total DNA of MCM-producing Streptomyces macromomyceticus M480-M1 yielded a 2.6-kb fragment that hybridized strongly to the probes. The hybridized probe was stable to washing with 3 x SSC at 75 degrees C. Radioactivity derived from the hybridized probe was comparable to that expected theoretically from hybridization between the probe and the true target sequence. The 2.6-kb fragment was cloned into Escherichia coli RR1 with pBR322 and subsequently subcloned into Streptomyces lividans TK21 with pIJ702. Nucleotide sequence analysis of the cloned fragment verified the existence of the sequence corresponding to the amino acid sequence of MCM apoprotein and about 90% homologies with the probes. Thus, the use of relatively long deoxynucleotide probes with arbitrarily chosen C or G for the third letters will be advantageous in cloning Streptomyces protein genes where more than 90% of the third letters have been known to be C or G. In addition, theoretical diagnosis of hybridization should be a great help to distinguish true positives from false ones.