• Title, Summary, Keyword: antibiotic biosynthesis

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Mechanisms of Self-protection and Genes Coding for Antibiotic Biosynthesis, Particularly, in Microorganisms which Produce Antibiotic Inhibitors of Protein Synthesis (항생물질생산균(抗生物質生産菌)의 단백질합성계조해항생물질(蛋白質合性系阻害抗生物質)에 대한 자기내성기구(自己耐性機構)와 생합성유전자(生合成遺傳子))

  • Paik, Soon-Young;Sugiyama, Masanori;Yang, Han-Chul
    • Applied Biological Chemistry
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    • v.31 no.4
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    • pp.371-375
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    • 1988
  • Streptomycetes are attractive microorganisms for their production of various secondary metabolites such as antibiotics. Now, the development of gene manipulation in this microorganisms enables the cloning and analysis of the genes which coding for antibiotic biosynthesis and resistance to the drug. In this article, we reviewed the studies with respect to the mechanisms of self-protection and cloning of the genes cloning for antibiotic biosynthesis, particularly, in microorganisms which produce antibiotic inhibitors of protein synthesis.

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Mechanism of Antibiotic Action and Biosynthesis of Centipedin Purified from Scolopendra subspinipes multilans L. Koch (Centipede)

  • Kim, Ki-Tae;Hong, Sa-Weon;Lee, Jong-Ho;Park, Kyung-Bae;Cho, Key-Seung
    • BMB Reports
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    • v.31 no.4
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    • pp.328-332
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    • 1998
  • The 8-hydroxyisocoumarin, named Centipedin, which has a significant antibiotic activity, was separated and solubilized with organic solvents, such as diethyl ether from centipede Scolopendra subspinipes multilans L. Koch. The Centipedin was purified by silicic acid column and high S cation exchange chromatography followed by reverse-phase HPLC. It was confirmed that Centipedin has a potent antibiotic effectiveness against Gram-negative Klebsiella pneumoniae ATCC 8308. The results showed that Centipedin blocks both DNA replication and RNA transcription during the growth of this pathogen in vivo. The biosynthesis of antibiotic 8-hydroxyisocoumarin was studied in vivo by feeding $[^{14}C]-labelled$ compound as a precursor to live centipede, in which $[^{14}C]acetate$ was the most efficiently incorporated into the Centipedin within 30 h after injection. Also, in vitro study on the biosynthesis of Centipedin showed that efficient incorporation of $[^{14}C]acetate$ occurred at pH range 5.0-7.0 for 10 h incubation and decreased significantly after then. It is suggested that 8-hydroxyisocoumarin is one of the defense compounds acting on bacterial infection in Scolopendra subspinipes.

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S-Adenosylmethionine (SAM) Regulates Antibiotic Biosynthesis in Streptomyces spp. in a Mode Independent of Its Role as a Methyl Donor

  • Zhao Xin-Qing;Jin Ying-Yu;Kwon Hyung-Jin;Yang Young-Yell;Suh Joo-Won
    • Journal of Microbiology and Biotechnology
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    • v.16 no.6
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    • pp.927-932
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    • 2006
  • S-Adenosylmethionine (SAM) is a ubiquitous biomolecule serving mainly as a methyl donor. Our recent studies revealed that SAM controls antibiotic production in Streptomyces. In this study, the functional mode of SAM was studied in S. coelicolor and S. antibioticus ATCC11891, employing S-adenosylhomocysteine (SAH), a methylation reaction product of SAM. Actinorhodin biosynthesis did not require SAM as a methyl donor, whereas SAH enhanced the actinorhodin biosynthesis up to the level comparable to SAM, and the most effective concentration of SAH was higher than that of SAM. In the case of oleandomycin that requires SAM for its biosynthesis, both SAM and SAH at the concentration as low as 100 mM showed comparable efficacy in enhancing the production; SAM at 1 mM concentration additionally stimulated to give a 5-fold enhancement of oleandomycin production. In vitro autophosphorylation of protein kinase AfsK was found to be activated by both SAM and SAH, as well as other structurally related compounds. Our studies demonstrate that SAM regulates antibiotic biosynthesis in a mode independent of its role as a methyl donor and suggest that SAM acts directly as an intracellular signaling molecule for Streptomyces.

Proteomics-driven Identification of Putative AfsR2-target Proteins Stimulating Antibiotic Biosynthesis in Streptomyces lividans

  • Kim Chang-Young;Park Hyun-Joo;Kim Eung-Soo
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.10 no.3
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    • pp.248-253
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    • 2005
  • AfsR2, originally identified from Streptomyces lividans, is a global regulatory protein which stimulates antibiotic biosynthesis. Through its stable chromosomal integration, the high level of gene expression of afsR2 significantly induced antibiotic production as well as the sporulation of S. lividans, implying the presence of yet-uncharacterized AfsR2-target proteins. To identify and evaluate the putative AfsR2-target proteins involved in antibiotic regulation, the proteomics-driven approach was applied to the wild-type S. lividans and the afsR2-integrated actinorhodin overproducing strain. The 20 gel-electrophoresis gave approximately 340 protein spots showing different protein expression patterns between these two S. lividans strains. Further MALDI-TOF analysis revealed several AfsR2-target proteins, including glyceraldehyde-3-phosphate dehydrogenase, putative phosphate transport system regulator, guanosine penta phosphate synthetase/polyribonucleotide nucleotidyltransferase, and superoxide dismutase, which suggests that the AfsR2 should be a pleiotropic regulatory protein which controls differential expressions of various kinds of genes in Streptomyces species.

Biosynthetic Gene Cluster of Cephabacin for the Combinatorial Biosynthesis of $\beta$-Lactam Antibiotics

  • Chang, Hyun-Sung;Park, Myoung-Jin;Atanas Demirev;Nam, Doo-Hyun
    • Proceedings of the PSK Conference
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    • pp.85-87
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    • 2003
  • $\beta$-Lactams are historically and clinically representative antibiotics used for therapeutic purposes. In early days, penicillin (penam antibiotic) and cephalosporin (cephem antibiotic) were found in culture broth of two different filamentous fungi, Penicillium chrysogenum and Acremonium chrysogenum. Since 1970, a variety of $\beta$-lactam structures have been discovered from bacterial cultures including Streptomyces species, which are known as cephamycin, cephabacin (cephem antibiotics), clavulanic acid (oxopenam antibiotic), thienamycin (carbapenem antibiotic), and sulfazecin (monobactam antibiotic). (omitted)

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Cloning and Characterization of a Gene Cluster for the Production of Polyketide Macrolide Dihydrochalcomycin in Streptomyces sp. KCTC 0041BP

  • Jaishy Bharat Prasad;Lim Si-Kyu;Yoo Ick-Dong;Yoo Jin-Cheol;Sohng Jae-Kyung;Nam Doo-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.16 no.5
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    • pp.764-770
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    • 2006
  • Dihydrochalcomycin (GERI-155), produced by Streptomyces sp. KCTC-0041BP isolated from Korean soil, is a 16-membered macrolide antibiotic consisting of two deoxysugar moieties at C-5 and C-20 positions of a branched lactone ring. The cloning and sequencing of a gene cluster for dihydrochalcomycin biosynthesis revealed a 63-kb nucleotide region containing 25 open reading frames (ORFs). The products of all of these 25 ORFs playa role in dihydrochalcomycin biosynthesis and self-resistance against the compounds synthesized. At the core of this cluster lies a 39.6-kb polyketide synthase (PKS) region encoding eight modules in five giant multifunctional protein-coding genes (gerSI-SV). The genes responsible for the biosynthesis of deoxysugar moieties, D-chalcose and D-mycinose, and their modification and attachment were found on either side of this PKS region. The involvement of this gene cluster in dihydrochalcomycin biosynthesis was confirmed by disruption of the dehydratase (DH) domain in module 3 of the PKS gene and by metabolite analysis.

Control of Tylosin Biosynthesis in Streptomyces fradiae

  • Cundliffe, Eric
    • Journal of Microbiology and Biotechnology
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    • v.18 no.9
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    • pp.1485-1491
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    • 2008
  • Tylosin biosynthesis is controlled in cascade fashion by multiple transcriptional regulators, acting positively or negatively, in conjunction with a signalling ligand that acts as a classical inducer. The roles of regulatory gene products have been characterized by a combination of gene expression analysis and fermentation studies, using engineered strains of S. fradiae in which specific genes were inactivated or overexpressed. Among various novel features of the regulatory model, involvement of the signalling ligand is not essential for tylosin biosynthesis.

Improvement of Natamycin Production by Cholesterol Oxidase Overexpression in Streptomyces gilvosporeus

  • Wang, Miao;Wang, Shaohua;Zong, Gongli;Hou, Zhongwen;Liu, Fei;Liao, D. Joshua;Zhu, Xiqiang
    • Journal of Microbiology and Biotechnology
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    • v.26 no.2
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    • pp.241-247
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    • 2016
  • Natamycin is a widely used antifungal antibiotic. For natamycin biosynthesis, the gene pimE encodes cholesterol oxidase, which acts as a signalling protein. To confirm the positive effect of the gene pimE on natamycin biosynthesis, an additional copy of the gene pimE was inserted into the genome of Streptomyces gilvosporeus 712 under the control of the ermE* promoter (permE*) using intergeneric conjugation. Overexpression of the target protein engendered 72% and 81% increases in the natamycin production and cell productivity, respectively, compared with the control strain. Further improvement in the antibiotic production was achieved in a 1 L fermenter to 7.0 g/l, which was a 153% improvement after 120 h cultivation. Exconjugants highly expressing pimE and pimM were constructed to investigate the effects of both genes on the increase of natamycin production. However, the co-effect of pimE and pimM did not enhance the antibiotic production obviously, compared with the exconjugants highly expressing pimE only. These results suggest not only a new application of cholesterol oxidase but also a useful strategy to genetically engineer natamycin production.