| 1. |
Ostash B,
Rebets Y,
Yuskevich V,
Luzhetskyy A,
Tkachenko V,
Fedorenko V,
( 2003 ) Targeted disruption of Streptomyces globisporus lndF and lndL cyclase genes involved in landomycin E biosynthesis. PMID : 14533479 : DOI : 10.1007/bf02931329 Abstract >>
Streptomyces globisporus strains with knockouts in lndF and lndL genes, previously identified as possibly encoding cyclases governing cyclization of the nascent oligoketide ('polyketide') chain during the biosynthesis of the antitumor angucycline landomycin E, were prepared. On combining the results of sequence analysis and HPLC of extracts from mutant strains, lndL was suggested to control the first cyclization-aromatization event and lndF to be responsible for the 3rd-4th ring formation.
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2. |
Sakata N,
Ikeno S,
Hori M,
Hamada M,
Otani T,
( 1992 ) Cloning and nucleotide sequencing of the antitumor antibiotic C-1027 apoprotein gene. PMID : 1369059 : DOI : 10.1271/bbb.56.1592 Abstract >>
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.
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3. |
Otani T,
Yasuhara T,
Minami Y,
Shimazu T,
Zhang R,
Xie MY,
( 1991 ) Purification and primary structure of C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, from Streptomyces globisporus. PMID : 1368692 : Abstract >>
C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, was isolated by column chromatography on DEAE-cellulose, butyl-Toyopearl and Sephadex G-50 from a culture filtrate of Streptomyces globisporus. The amino acid sequence of purified C-1027-AG was determined with a protein sequencer on the basis of fragment peptides obtained by enzymatic hydrolysis with lysylendopeptidase, V8 protease, endopeptidase AspN and chymotrypsin, after performic acid oxidation. C-1027-AG is shown to consist of a single polypeptide chain cross-linked by two disulfide bonds, and to contain a total of 110 amino acid residues with alanine and glycine as its amino- and carboxyl-termini, respectively; its molecular weight was calculated to be 10,500 daltons. The primary structure of C-1027-AG is indicated to be identical to the protein moiety of C-1027, and is highly homologous to the sequences of antitumor proteins obtained from other Streptomyces species.
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4. |
Liu W,
Christenson SD,
Standage S,
Shen B,
( 2002 ) Biosynthesis of the enediyne antitumor antibiotic C-1027. PMID : 12183628 : DOI : 10.1126/science.1072110 Abstract >>
C-1027 is a potent antitumor agent with a previously undescribed molecular architecture and mode of action. Cloning and characterization of the 85-kilobase C-1027 biosynthesis gene cluster from Streptomyces globisporus revealed (i) an iterative type I polyketide synthase that is distinct from any bacterial polyketide synthases known to date, (ii) a general polyketide pathway for the biosynthesis of both the 9- and 10-membered enediyne antibiotics, and (iii) a convergent biosynthetic strategy for the C-1027 chromophore from four building blocks. Manipulation of genes governing C-1027 biosynthesis allowed us to produce an enediyne compound in a predicted manner.
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5. |
Liu W,
( 2000 ) Genes for production of the enediyne antitumor antibiotic C-1027 in Streptomyces globisporus are clustered with the cagA gene that encodes the C-1027 apoprotein. PMID : 10639366 : DOI : 10.1128/aac.44.2.382-392.2000 PMC : PMC89687 Abstract >>
C-1027, the most potent member of the enediyne antitumor antibiotic family, is produced by Streptomyces globisporus C-1027 and consists of an apoprotein (encoded by the cagA gene) and a nonpeptidic chromophore. The C-1027 chromophore could be viewed as being derived biosynthetically from a benzoxazolinate, a deoxyamino hexose, a beta-amino acid, and an enediyne core. By adopting a strategy for cloning of the C-1027 biosynthesis gene cluster by mapping a putative dNDP-glucose 4,6-dehydratase (NGDH) gene to cagA, we have localized 75 kb of contiguous DNA from S. globisporus. DNA sequence analysis of two regions of the cloned gene cluster revealed two genes, sgcA and sgcB, that encode an NGDH enzyme and a transmembrane efflux protein, respectively, and confirmed that the cagA gene resides approximately 14 kb upstream of the sgcAB locus. The involvement of the cloned gene cluster in C-1027 biosynthesis was demonstrated by disrupting the sgcA gene to generate C-1027-nonproducing mutants and by complementing the sgcA mutants in vivo to restore C-1027 production. These results represent the first cloning of a gene cluster for enediyne antitumor antibiotic biosynthesis and provide a starting point for future genetic and biochemical investigations of C-1027 biosynthesis.
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6. |
Christianson CV,
Montavon TJ,
Van Lanen SG,
Shen B,
Bruner SD,
( 2007 ) The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway. PMID : 17516659 : DOI : 10.1021/bi7003685 Abstract >>
The SgcC4 l-tyrosine 2,3-aminomutase (SgTAM) catalyzes the formation of (S)-beta-tyrosine in the biosynthetic pathway of the enediyne antitumor antibiotic C-1027. SgTAM is homologous to the histidine ammonia lyase family of enzymes whose activity is dependent on the methylideneimidazole-5-one (MIO) cofactor. Unlike the lyase enzymes, SgTAM catalyzes additional chemical transformations resulting in an overall stereospecific 1,2-amino shift in the substrate l-tyrosine to generate (S)-beta-tyrosine. Previously, we provided kinetic, spectroscopic, and mutagenesis data supporting the presence of MIO in the active site of SgTAM [Christenson, S. D.; Wu, W.; Spies, A.; Shen, B.; and Toney, M. D. (2003) Biochemistry 42, 12708-12718]. Here we report the first X-ray crystal structure of an MIO-containing aminomutase, SgTAM, and confirm the structural homology of SgTAM to ammonia lyases. Comparison of the structure of SgTAM to the l-tyrosine ammonia lyase from Rhodobacter sphaeroides provides insight into the structural basis for aminomutase activity. The results show that SgTAM has a closed active site well suited to retain ammonia and minimize the formation of lyase elimination products. The amino acid determinants for substrate recognition and catalysis can be predicted from the structure, setting the framework for detailed mechanistic investigations.
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7. |
Zhu L,
Ostash B,
Rix U,
Nur-E-Alam M,
Mayers A,
Luzhetskyy A,
Mendez C,
Salas JA,
Bechthold A,
Fedorenko V,
Rohr J,
( 2005 ) Identification of the function of gene lndM2 encoding a bifunctional oxygenase-reductase involved in the biosynthesis of the antitumor antibiotic landomycin E by Streptomyces globisporus 1912 supports the originally assigned structure for landomycinone. PMID : 15651811 : DOI : 10.1021/jo0483623 PMC : PMC2884283 Abstract >>
The angucycline antibiotic family of the landomycins displays potent antitumor activity. To elucidate early post polyketide synthase (PKS) tailoring steps of the landomycin E biosynthetic pathway in Streptomyces globisporus 1912, the mutant S. globisporus M12 was prepared through gene replacement experiment of lndM2. It encodes an enzyme with putative oxygenase and reductase domains, according to sequencing of the gene and its counterpart lanM2 from S. cyanogenus S136 landomycin A biosynthetic gene cluster. The isolation of the novel shunt products 11-hydroxytetrangomycin and 4-hydroxytetrangomycin along with the well-known angucyclines tetrangomycin and tetrangulol from the culture of S. globisporus M12 provides evidence for the involvement of lndM2 in the early biosynthetic pathway of the landomycins, in particular in the formation of the alicyclic 6-hydroxy function of the landomycin aglycon. We therefore propose LndM2 to be responsible for both hydroxylation of the 6-position and its subsequent reduction. These reactions are necessary before the glycosylation reactions can occur. The results are in agreement with the originally published structure of landomycin but do not support the recently suggested revised structure.
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8. |
Rebets Y,
Ostash B,
Luzhetskyy A,
Kushnir S,
Fukuhara M,
Bechthold A,
Nashimoto M,
Nakamura T,
Fedorenko V,
( 2005 ) DNA-binding activity of LndI protein and temporal expression of the gene that upregulates landomycin E production in Streptomyces globisporus 1912. PMID : 15632445 : DOI : 10.1099/mic.0.27244-0 Abstract >>
The gene lndI is involved in the pathway-specific positive regulation of biosynthesis of the antitumour polyketide landomycin E in Streptomyces globisporus 1912. LndI was overexpressed in Escherichia coli as a protein C-terminally fused to the intein-chitin-binding-domain tag and purified in a one-step column procedure. Results of in vivo LndI titration, DNA gel mobility-shift assays and promoter-probing experiments indicate that LndI is an autoregulatory DNA-binding protein that binds to its own gene promoter and to the promoter of the structural gene lndE. Enhanced green fluorescent protein was used as a reporter to study the temporal and spatial pattern of lndI transcription. Expression of lndI started before cells entered mid-exponential phase and peak expression coincided with maximal accumulation of landomycin E and biomass. In solid-phase analysis, lndI expression was evident in substrate mycelia but was absent from aerial hyphae and spores.
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9. |
Ostash B,
Rix U,
Rix LL,
Liu T,
Lombo F,
Luzhetskyy A,
Gromyko O,
Wang C,
Braña AF,
Méndez C,
Salas JA,
Fedorenko V,
Rohr J,
( 2004 ) Generation of new landomycins by combinatorial biosynthetic manipulation of the LndGT4 gene of the landomycin E cluster in S. globisporus. PMID : 15123249 : DOI : 10.1016/j.chembiol.2004.03.011 Abstract >>
A 3 kb DNA fragment from the Streptomyces globisporus 1912 landomycin E (LaE) biosynthetic gene cluster (lnd) was completely sequenced. Three open reading frames were identified, lndGT4, lndZ4, and lndZ5, whose probable translation products resemble a glycosyltransferase, a reductase, and a hydroxylase, respectively. Studies of generated mutants from disruption and complementation experiments involving the lndGT4 gene allowed us to determine that LndGT4 controls the terminal L-rhodinose sugar attachment during LaE biosynthesis and that LndZ4/LndZ5 are responsible for the unique C11-hydroxylation of the landomycins. Generation of the novel landomycins F, G, and H in the course of these studies provided evidence for the flexibility of lnd glycosyltransferases toward their acceptor substrates and a basis for initial structure-activity relationships within the landomycin family of antibiotics.
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10. |
Kim BJ,
Kim CJ,
Chun J,
Koh YH,
Lee SH,
Hyun JW,
Cha CY,
Kook YH,
( 2004 ) Phylogenetic analysis of the genera Streptomyces and Kitasatospora based on partial RNA polymerase beta-subunit gene (rpoB) sequences. PMID : 15023980 : DOI : 10.1099/ijs.0.02941-0 Abstract >>
The RNA polymerase beta-subunit genes (rpoB) of 67 Streptomyces strains, representing 57 species, five Kitasatospora strains and Micromonospora echinospora KCTC 9549 were partially sequenced using a pair of rpoB PCR primers. Among the streptomycetes, 99.7-100 % similarity within the same species and 90.2-99.3 % similarity at the interspecific level were observed by analysis of the determined rpoB sequences. The topology of the phylogenetic tree based on rpoB sequences was similar to that of 16S rDNA. The five Kitasatospora strains formed a stable monophyletic clade and a sister group to the clade comprising all Streptomyces species. Although there were several discrepancies in the details, considerable agreement was found between the results of rpoB analysis and those of numerical phenetic classification. This study demonstrates that analysis of rpoB can be used as an alternative genetic method in parallel to conventional taxonomic methods, including numerical phenetic and 16S rDNA analyses, for the phylogenetic analyses of the genera Streptomyces and Kitasatospora.
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11. |
Ostash B,
Rebets Y,
Myronovskyy M,
Tsypik O,
Ostash I,
Kulachkovskyy O,
Datsyuk Y,
Nakamura T,
Walker S,
Fedorenko V,
( 2011 ) Identification and characterization of the Streptomyces globisporus 1912 regulatory gene lndYR that affects sporulation and antibiotic production. PMID : 21292750 : DOI : 10.1099/mic.0.045088-0 PMC : PMC3139444 Abstract >>
Here, we report the identification and functional characterization of the Streptomyces globisporus 1912 gene lndYR, which encodes a GntR-like regulator of the YtrA subfamily. Disruption of lndYR arrested sporulation and antibiotic production in S. globisporus. The results of in vivo and in vitro studies revealed that the ABC transporter genes lndW-lndW2 are targets of LndYR repressive action. In Streptomyces coelicolor M145, lndYR overexpression caused a significant increase in the amount of extracellular actinorhodin. We suggest that lndYR controls the transcription of transport system genes in response to an as-yet-unidentified signal. Features that distinguish lndYR-based regulation from other known regulators are discussed.
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12. |
Cooke HA,
Bruner SD,
( 2010 ) Probing the active site of MIO-dependent aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites. PMID : 20577998 : DOI : 10.1002/bip.21500 PMC : PMC3419534 Abstract >>
The tyrosine aminomutase SgTAM produces (S)-ss-tyrosine from L-tyrosine in the biosynthesis of the enediyne antitumor antibiotic C-1027. This conversion is promoted by the methylideneimidazole-5-one (MIO) prosthetic group. MIO was first identified in the homologous family of ammonia lyases, which deaminate aromatic amino acids to form alpha,ss-unsaturated carboxylates. Studies of substrate specificity have been described for lyases but there have been limited reports in altering the substrate specificity of aminomutases. Furthermore, it remains unclear as to what structural properties are responsible for catalyzing the presumed readdition of the amino group into the alpha,ss-unsaturated intermediates to form ss-amino acids. Attempts to elucidate specificity and mechanistic determinants of SgTAM have also proved to be difficult as it is recalcitrant to perturbations to the active site via mutagenesis. An X-ray cocrystal structure of the SgTAM mutant of the catalytic base with L-tyrosine verified important substrate binding residues as well as the enzymatic base. Further mutagenesis revealed that removal of these crucial interactions renders the enzyme inactive. Proposed structural determinants for mutase activity probed via mutagenesis, time-point assays and X-ray crystallography revealed a complicated role for these residues in maintaining key quaternary structure properties that aid in catalysis.
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13. |
Ostash I,
Rebets Y,
Ostash B,
Kobylyanskyy A,
Myronovskyy M,
Nakamura T,
Walker S,
Fedorenko V,
( 2008 ) An ABC transporter encoding gene lndW confers resistance to landomycin E. PMID : 18369595 : DOI : 10.1007/s00203-008-0367-5 Abstract >>
Streptomyces globisporus 1912 produces a polyketide antibiotic landomycin E (LaE), which possesses anticancer activity. A 1.8 kb DNA fragment at the end of landomycin E biosynthetic gene cluster was sequenced. DNA sequence analysis of this fragment identified one complete open reading frame, designated lndW. The deduced sequence of lndW gene product revealed significant similarity to the ATP-binding domains of the ABC (ATP-binding protein cassette) superfamily of transport-related proteins. Knockout of lndW had no significant effect on resistance to LaE and its production. The expression of lndW in S. globisporus 1912 was proven via transcriptional fusion of lndW promoter to EGFP (enhanced green fluorescent protein). Overexpression of lndW in S. lividans TK24 conferred resistance to LaE. The mechanism of lndW function in LaE biosynthesis is discussed.
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14. |
Van Lanen SG,
Lin S,
Shen B,
( 2008 ) Biosynthesis of the enediyne antitumor antibiotic C-1027 involves a new branching point in chorismate metabolism. PMID : 18182490 : DOI : 10.1073/pnas.0708750105 PMC : PMC2206564 Abstract >>
C-1027 is an enediyne antitumor antibiotic composed of four distinct moieties: an enediyne core, a deoxy aminosugar, a beta-amino acid, and a benzoxazolinate moiety. We now show that the benzoxazolinate moiety is derived from chorismate by the sequential action of two enzymes-SgcD, a 2-amino-2-deoxyisochorismate (ADIC) synthase and SgcG, an iron-sulfur, FMN-dependent ADIC dehydrogenase-to generate 3-enolpyruvoylanthranilate (OPA), a new intermediate in chorismate metabolism. The functional elucidation and catalytic properties of each enzyme are described, including spectroscopic characterization of the products and the development of a fluorescence-based assay for kinetic analysis. SgcD joins isochorismate (IC) synthase and 4-amino-4-deoxychorismate (ADC) synthase as anthranilate synthase component I (ASI) homologues that are devoid of pyruvate lyase activity inherent in ASI; yet, in contrast to IC and ADC synthase, SgcD has retained the ability to aminate chorismate identically to that observed for ASI. The net conversion of chorismate to OPA by the tandem action of SgcD and SgcG unambiguously establishes a new branching point in chorismate metabolism.
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15. |
Montavon TJ,
Christianson CV,
Festin GM,
Shen B,
Bruner SD,
( 2008 ) Design and characterization of mechanism-based inhibitors for the tyrosine aminomutase SgTAM. PMID : 18078753 : DOI : 10.1016/j.bmcl.2007.11.046 PMC : PMC6312385 Abstract >>
The synthesis and evaluation of two classes of inhibitors for SgTAM, a 4-methylideneimidazole-5-one (MIO) containing tyrosine aminomutase, are described. A mechanism-based strategy was used to design analogs that mimic the substrate or product of the reaction and form covalent interactions with the enzyme through the MIO prosthetic group. The analogs were characterized by measuring inhibition constants and X-ray crystallographic structural analysis of the co-complexes bound to the aminomutase, SgTAM.
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16. |
Chang CY,
Lohman JR,
Cao H,
Tan K,
Rudolf JD,
Ma M,
Xu W,
Bingman CA,
Yennamalli RM,
Bigelow L,
Babnigg G,
Yan X,
Joachimiak A,
Phillips GN,
Shen B,
( 2016 ) Crystal Structures of SgcE6 and SgcC, the Two-Component Monooxygenase That Catalyzes Hydroxylation of a Carrier Protein-Tethered Substrate during the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 in Streptomyces globisporus. PMID : 27560143 : DOI : 10.1021/acs.biochem.6b00713 PMC : PMC5024704 Abstract >>
C-1027 is a chromoprotein enediyne antitumor antibiotic produced by Streptomyces globisporus. In the last step of biosynthesis of the (S)-3-chloro-5-hydroxy-�]-tyrosine moiety of the C-1027 enediyne chromophore, SgcE6 and SgcC compose a two-component monooxygenase that hydroxylates the C-5 position of (S)-3-chloro-�]-tyrosine. This two-component monooxygenase is remarkable for two reasons. (i) SgcE6 specifically reacts with FAD and NADH, and (ii) SgcC is active with only the peptidyl carrier protein (PCP)-tethered substrate. To address the molecular details of substrate specificity, we determined the crystal structures of SgcE6 and SgcC at 1.66 and 2.63 ? resolution, respectively. SgcE6 shares a similar �]-barrel fold with the class I HpaC-like flavin reductases. A flexible loop near the active site of SgcE6 plays a role in FAD binding, likely by providing sufficient space to accommodate the AMP moiety of FAD, when compared to that of FMN-utilizing homologues. SgcC shows structural similarity to a few other known FADH2-dependent monooxygenases and sheds light on some biochemically but not structurally characterized homologues. The crystal structures reported here provide insights into substrate specificity, and comparison with homologues provides a catalytic mechanism of the two-component, FADH2-dependent monooxygenase (SgcE6 and SgcC) that catalyzes the hydroxylation of a PCP-tethered substrate.
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17. |
Huang T,
Chang CY,
Lohman JR,
Rudolf JD,
Kim Y,
Chang C,
Yang D,
Ma M,
Yan X,
Crnovcic I,
Bigelow L,
Clancy S,
Bingman CA,
Yennamalli RM,
Babnigg G,
Joachimiak A,
Phillips GN,
Shen B,
( 2016 ) Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027. PMID : 27406907 : DOI : 10.1038/ja.2016.88 PMC : PMC5083130 Abstract >>
Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us to propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase-associated enzymes, into an enzyme-sequestered enediyne core intermediate. These findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.
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18. |
Kim KO,
Shin KS,
Kim MN,
Shin KS,
Labeda DP,
Han JH,
Kim SB,
( 2012 ) Reassessment of the status of Streptomyces setonii and reclassification of Streptomyces fimicarius as a later synonym of Streptomyces setonii and Streptomyces albovinaceus as a later synonym of Streptomyces globisporus based on combined 16S rRNA/gyrB gene sequence analysis. PMID : 22286909 : DOI : 10.1099/ijs.0.040287-0 DOI : 10.1099/ijs.0.040287-0 Abstract >>
The 16S rRNA and gyrB genes of 22 Streptomyces strains belonging to the Streptomyces griseus cluster were sequenced, and their taxonomic positions were re-evaluated. For correct analysis, all of the publicly available sequences of the species were collected and compared with those obtained in this study. Species for which no consensus sequence could be identified were excluded from the phylogenetic analysis. The levels of 16S rRNA gene sequence similarity within the cluster ranged from 98.6 to 100% with a mean value of 99.6 �� 0.3%, and those of the gyrB gene ranged from 93.6 to 99.9% with a mean value of 96.3 �� 1.5%. The observed average nucleotide substitution rate of the gyrB gene was ten times higher than that of the 16S rRNA gene, showing a far higher degree of variation. Strains sharing 99.3% or more gyrB sequence similarity (corresponding to an evolutionary distance of 0.0073) always formed monophyletic groups in both trees. Through the combined analysis of the two genes, clear cases of synonymy could be identified and, according to the priority rule, the assertion of the status of Streptomyces setonii as a distinct species and the reclassification of Streptomyces fimicarius as a later synonym of S. setonii and Streptomyces albovinaceus as a later synonym of Streptomyces globisporus are proposed. Emended descriptions of S. setonii and S. globisporus are provided.
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19. |
( 1993 ) The amino acid sequence of actinoxanthin apoprotein deduced from the base sequence of the gene. PMID : 8226326 : DOI : 10.7164/antibiotics.46.1475 Abstract >>
N/A
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20. |
( 1993 ) Some characteristics of DNA strand scission by macromolecular antitumor antibiotic C-1027 containing a novel enediyne chromophore. PMID : 8504075 : DOI : 10.1021/bi00072a008 Abstract >>
A new macromolecular antitumor antibiotic, C-1027, shows potent cytotoxic effects and DNA cutting activity. The DNA cleaving properties of C-1027 are compared with those of other enediyne compounds such as neocarzinostatin, esperamicin A1, and calicheamicin gamma 1. Even in the absence of thiols or reductants, the antibiotic C-1027 has high DNA breakage ability. Of special interest is the fact that C-1027 causes strand breaks two base pairs apart at specific sites such as 5'-TAT/3'-ATA and 5'-AGA/3'-TCT (cleavage sites in italics) in the two strands. This novel double-stranded cleavage fashion is different from that of calicheamicin gamma 1, which is found to have a 3-bp separation between cleavage sites on the two strands. The asymmetric cleavage pattern to the 3'-side and a competitive experiment with distamycin A reveal minor-groove interaction of double-helical DNA with C-1027. This antibiotic appears to oxidize DNA through hydrogen abstraction predominantly at the C-4' carbon of deoxyribose. The activation mechanism of C-1027, which contains an enediyne chromophore of the esperamicin/calicheamicin type, has been proposed.
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21. |
( 1976 ) Chemical studies on actinoxanthin. PMID : 994323 : DOI : 10.7164/antibiotics.29.1026 Abstract >>
The antitumor protein actinoxanthin exhibits high inhibitory activity against a number of gram-positive bacteria and some strains of transplantable leucoses and related tumors. Actinoxanthin was shown to consist of a single polypeptide chain crosslinked by two disulfide bonds and to contain 107 amino acid residues. Reduced and alkylated actinoxanthin was digested with chymotrypsin, thermolysin and trypsin. Based on the sequence analysis of fragments so obtained the complete amino acid sequence and the location of disulfide bonds of actinoxanthin has been proposed. The high degree homology of some regions of actinoxanthin and the antitumor protein neocarzinostatin have been revealed.
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22. |
( 1990 ) Cloning and nucleotide sequence of the N-acetylmuramidase M1-encoding gene from Streptomyces globisporus. PMID : 2341041 : DOI : 10.1016/0378-1119(90)90062-v Abstract >>
The gene (acm) encoding N-acetylmuramidase M1 (ACM) was cloned of Streptomyces globisporus ATCC No. 21553. The nucleotide sequence of the acm gene was determined and found to code for an ORF of 294 amino acids (aa). Comparison of aa sequence deduced from the acm gene with the N-terminal sequence of the extracellular enzyme suggests that ACM is synthesized with a 77-aa leader peptide. A comparison of the ACM aa sequence with the aa sequences of other proteins in the NBRF data base reveals that ACM has strong similarity to the N-O-diacetylmuramidase secreted by the fungus Chalaropsis.
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