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      Draft Genome Sequence of Teicoplanin-Producing Strain Actinoplanes teichomyceticus CPCC 203265

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          Abstract

          We report here the draft genome sequence of Actinoplanes teichomyceticus CPCC 203265, a producer of glycopeptide antibiotic teicoplanin, which has significant inhibitory activity against multidrug-resistant Gram-positive pathogens. The draft genome size is 8 Mb, with a G+C content of 72.8%, and its sequence will facilitate the genome exploration of novel secondary metabolites.

          ABSTRACT

          We report here the draft genome sequence of Actinoplanes teichomyceticus CPCC 203265, a producer of glycopeptide antibiotic teicoplanin, which has significant inhibitory activity against multidrug-resistant Gram-positive pathogens. The draft genome size is 8 Mb, with a G+C content of 72.8%, and its sequence will facilitate the genome exploration of novel secondary metabolites.

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          Teicoplanin, a new antibiotic from Actinoplanes teichomyceticus nov. sp.

          S Somma, L. Gastaldo, A. Corti (1984)
          Teicoplanin, a new glycopeptide antibiotic belonging to the same family as vancomycin, inhibits cell wall synthesis in Bacillus subtilis; the inhibition is accompanied by an intracellular accumulation of UDP-N-acetyl-muramyl-pentapeptide. A cell-free system from Bacillus stearothermophilus, capable of synthesizing peptidoglycan, is 50% inhibited by teicoplanin at 40 micrograms/ml and 100% inhibited at 100 micrograms/ml; suppression of peptidoglycan synthesis is accompanied by parallel accumulation of the lipid intermediate. Teicoplanin binds to cell walls and forms a complex with N,N'-diacetyl-L-lysyl-D-alanyl-D-alanine. The association constant of this complex is 2.56 X 10(6) liters mol-1, calculated by spectrophotometric titration. The mechanism of action of teicoplanin is discussed in comparison with those of other inhibitors of cell wall biosynthesis, namely, vancomycin, ristocetin, and gardimycin.
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            Organization of the teicoplanin gene cluster in Actinoplanes teichomyceticus.

            Stefano Donadio, Lubbert Dijkhuizen, Dario Bianchi … (2003)
            The glycopeptide teicoplanin is used for the treatment of serious infections caused by Gram-positive pathogens. The tcp gene cluster, devoted to teicoplanin biosynthesis in the actinomycete Actinoplanes teichomyceticus, was isolated and characterized. From sequence analysis, the tcp cluster spans approximately 73 kb and includes 39 ORFs participating in teicoplanin biosynthesis, regulation, resistance and export. Of these, 34 ORFs find a match in at least one of the five glycopeptide gene clusters previously characterized. Putative roles could be assigned for most of the tcp genes. The two glycosyltransferases responsible for attaching amino sugars to amino acids 4 and 6 of the teicoplanin aglycon were overexpressed in Escherichia coli and characterized. They both recognize N-acetylglucosamine as the substrate. tGtfA can add a sugar residue in the presence or absence of N-acetylglucosamine at amino acid 4, while tGtfB can only glycosylate the teicoplanin aglycon.
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              Biosynthetic gene cluster of the glycopeptide antibiotic teicoplanin: characterization of two glycosyltransferases and the key acyltransferase.

              Lin Li, Tatiana Mironenko, Peter F. Leadlay … (2003)
              The gene cluster encoding biosynthesis of the clinically important glycopeptide antibiotic teicoplanin has been cloned from Actinoplanes teichomyceticus. Forty-nine putative open reading frames (ORFs) were identified within an 89 kbp genetic locus and assigned roles in teicoplanin biosynthesis, export, resistance, and regulation. Two ORFs, designated orfs 1 and 10*, showed significant homology to known glycosyltransferases. When heterologously expressed in Escherichia coli, these glycosyltransferases were shown to catalyze the transfer of UDP-(N-acetyl)-glucosamine onto, respectively, 3-chloro-beta-hydroxytyrosine-6 (3-Cl-6betaHty) and 4-hydroxyphenylglycine-4 (4Hpg) of the teicoplanin heptapeptide aglycone. The product of another ORF, orf11*, was demonstrated in vitro to transfer n-acetyl-, n-butyryl-, and n-octanoyl-groups from acyl-CoA donors either to a free UDP-aminosugar or to an aminosugar moiety in the teicoplanin pseudoaglycone, thus identifying Orf11* as the key acyltransferase in teicoplanin maturation. These findings should accelerate the combinatorial engineering of new and improved glycopeptide drugs.
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                Author and article information

                Contributors
                Christina A. Cuomo: Role: Editor
                Journal
                Journal ID (nlm-ta): Microbiol Resour Announc
                Journal ID (iso-abbrev): Microbiol Resour Announc
                Journal ID (hwp): ga
                Journal ID (pmc): mra
                Journal ID (publisher-id): MRA
                Title: Microbiology Resource Announcements
                Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )
                ISSN (Electronic): 2576-098X
                Publication date (Electronic): 10 October 2019
                Publication date Collection: October 2019
                Volume: 8
                Issue: 41
                Electronic Location Identifier: e01091-19
                Affiliations
                [a ]NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
                [b ]CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
                Broad Institute
                Author notes
                Address correspondence to Lifei Wang, lifeiwang2002@ 123456hotmail.com , or Bin Hong, binhong69@ 123456hotmail.com .

                X. Li and C. Zhang contributed equally to this work.

                Citation Li X, Zhang C, Lei X, Wang L, Hong B. 2019. Draft genome sequence of teicoplanin-producing strain Actinoplanes teichomyceticus CPCC 203265. Microbiol Resour Announc 8:e01091-19. https://doi.org/10.1128/MRA.01091-19.

                Article
                Publisher ID: MRA01091-19
                DOI: 10.1128/MRA.01091-19
                PMC ID: 6787327
                PubMed ID: 31601670
                SO-VID: 9cc167e6-6be3-4ef7-b0a1-8dfc6511ac0e
                Copyright © Copyright © 2019 Li et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                Date received : 5 September 2019
                Date accepted : 25 September 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 7, Pages: 2, Words: 1173
                Funding
                Funded by: Drug Innovation Major Project of China;
                Award ID: 2018ZX09711001-007-001
                Award Recipient : Award Recipient : Award Recipient : Award Recipient :
                Funded by: Chinese Academy of Medical Sciences (CAMS), https://doi.org/10.13039/501100005150;
                Award ID: Innovation Fund for Medical Sciences 2018-I2M-3-005
                Award Recipient : Award Recipient : Award Recipient :
                Funded by: National Natural Science Foundation of China (NSF), https://doi.org/10.13039/501100001809;
                Award ID: 81703398
                Award ID: 81630089
                Award Recipient : Award Recipient : Award Recipient : Award Recipient :
                Funded by: Peking Union Medical College (PUMC), https://doi.org/10.13039/501100011176;
                Award ID: Youth Fund 332017080
                Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient :
                Categories
                Subject: Genome Sequences
                Custom metadata
                cover-date October 2019

                Data availability:

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