Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites.

  • Redenbach M
  • Kieser H
  • Denapaite D
 et al. 
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Abstract

Thiopeptides are ribosomally synthesized, posttranslationally modified peptides with potent activity against Gram-positives. However, only GE2270 has yielded semisynthetic derivatives under clinical investigations. The pbt gene cluster from the GE2270 producer Planobispora rosea was successfully expressed in the genetically tractable Nonomuraea ATCC39727. Gene deletions established that PbtO, PbtM1, PbtM2, PbtM3, and PbtM4 are involved in regiospecific hydroxylation and methylations of GE2270, leading to the generation of various derivatives with altered decorations. Further deletions established that PbtH and PbtG1 are involved in C-terminal amide and oxazoline formation, respectively. Surprisingly, preventing either step resulted in the accumulation of linear precursors in which the pyridine-generated macrocycle failed to form, and only one of the pyridine-forming serine residues had been dehydrated. Often, these linear precursors present a shortened C terminus but retain the full set of methylation and hydroxylation decorations.

Author-supplied keywords

  • 16S
  • Actinomycetales
  • Acyl Carrier Protein
  • Adenosine Triphosphate
  • Alkenes
  • Amino Acid
  • Amino Acid Sequence
  • Amino Acids
  • Aminobenzoates
  • Aminoglycosides
  • Aminoisobutyric Acids
  • Animals
  • Anti-Bacterial Agents
  • Antibiotics
  • Antimalarials
  • Antineoplastic
  • Antineoplastic Agents
  • Antiviral Agents
  • Aspartic Acid
  • Bacteria
  • Bacterial
  • Bacterial Infections
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Base Sequence
  • Benzoxazoles
  • Binding Sites
  • Biological Products
  • Biological Transport
  • Biopolymers
  • Biosynthetic Pathways
  • Biotechnology
  • Calcium
  • Carbon
  • Carboxylic Acids
  • Catalysis
  • Catalytic Domain
  • Cell Line
  • Cell Surface
  • Chemical
  • Chloroquine
  • Chromatography
  • Chromosome Mapping
  • Chromosomes
  • Cloning
  • Coenzyme A
  • Computational Biology
  • Corynebacterium diphtheriae
  • Cosmids
  • Crystallography
  • Culture Media
  • Cyclic
  • Cyclization
  • Cyclopentanes
  • DNA
  • DNA-Directed RNA Polymerases
  • Deferoxamine
  • Diamino
  • Disk Diffusion Antimicrobial Tests
  • Drug Resistance
  • Duplicate
  • Electrospray Ionization
  • Enediynes
  • Enzyme Inhibitors
  • Epoxide Hydrolases
  • Epoxy Compounds
  • Escherichia coli
  • Fluorinated
  • Fungal
  • Furans
  • Gene Deletion
  • Gene Dosage
  • Gene Expression
  • Gene Expression Regulation
  • Gene Knockout Techniques
  • Gene Library
  • Gene Order
  • Gene Silencing
  • Genes
  • Genetic
  • Genetic Complementation Test
  • Genetic Engineering
  • Genetic Markers
  • Genome
  • Genomic Library
  • Genomics
  • Glucans
  • Glucosides
  • Glycerol
  • Glycoside Hydrolases
  • Glycosylation
  • Glycosyltransferases
  • HCT116 Cells
  • Halomonas
  • High Pressure Liquid
  • Humans
  • Hydro-Lyases
  • Hydrocarbons
  • Hydroxybenzoates
  • Indoles
  • Insertional
  • Iron
  • Lactones
  • Lipase
  • Lipoproteins
  • Macrocyclic Compounds
  • Macrolides
  • Magnetic Resonance Spectroscopy
  • Malaria
  • Mass
  • Mass Spectrometry
  • Methylation
  • Methyltransferases
  • Methylurea Compounds
  • Mice
  • Micromonospora
  • Mixed Function Oxygenases
  • Models
  • Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Molecular Structure
  • Molecular Targeted Therapy
  • Molecular Typing
  • Multigene Family
  • Multiple
  • Mutagenesis
  • Mutation
  • Mycobacterium tuberculosis
  • NIH 3T3 Cells
  • Naphthalenes
  • Naphthalenesulfonates
  • Naphthols
  • Nocardia
  • Nucleic Acid
  • Oligopeptides
  • Open Reading Frames
  • Operon
  • Oxazoles
  • Oxidoreductases
  • Pactamycin
  • Pantothenic Acid
  • Peptide Elongation Factor Tu
  • Peptide Synthases
  • Peptides
  • Phylogeny
  • Plasmodium falciparum
  • Polyenes
  • Polyketide Synthases
  • Post-Translational
  • Promoter Regions
  • Protein Binding
  • Protein Biosynthesis
  • Protein Isoforms
  • Protein O-Methyltransferase
  • Protein Processing
  • Protein Structure
  • Pseudomonas
  • Pyridines
  • Pyrroles
  • RNA
  • Receptors
  • Recombination
  • Regulator
  • Repetitive Sequences
  • Restriction Mapping
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhizophoraceae
  • Ribosomal
  • S-Adenosylhomocysteine
  • S-Adenosylmethionine
  • Salicylates
  • Sequence Alignment
  • Sequence Analysis
  • Sequence Homology
  • Shikimic Acid
  • Siderophores
  • Spectrometry
  • Spiro Compounds
  • Staphylococcus aureus
  • Stereoisomerism
  • Streptomyces
  • Streptomyces coelicolor
  • Structure-Activity Relationship
  • Substrate Specificity
  • Sulfhydryl Compounds
  • Synteny
  • Synthetic
  • Terphenyl Compounds
  • Tertiary
  • Thiazoles
  • Time Factors
  • Transcriptional Activation
  • Transferases
  • Transformation
  • Tumor
  • X-Ray
  • Zinostatin
  • analogs & derivatives
  • antagonists & inhibitors
  • biosynthesis
  • chemical synthesis
  • chemistry
  • classification
  • cytology
  • deficiency
  • drug effects
  • drug therapy
  • enzymology
  • genetics
  • growth & development
  • isolation & purification
  • meta-Aminobenzoates
  • metabolism
  • methods
  • microbiology
  • para-Aminobenzoates
  • parasitology
  • pharmacology
  • physiology
  • toxicity

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Authors

  • M Redenbach

  • H M Kieser

  • D Denapaite

  • A Eichner

  • J Cullum

  • H Kinashi

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