Streptomyces
Encyclopedia
Streptomyces is the largest genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

 of Actinobacteria
Actinobacteria
Actinobacteria are a group of Gram-positive bacteria with high guanine and cytosine content. They can be terrestrial or aquatic. Actinobacteria is one of the dominant phyla of the bacteria....

 and the type genus of the family Streptomycetaceae
Streptomycetaceae
Streptomycetaceae is a family of Actinobacteria, making up to the monotypic suborder Streptomycineae. It includes the important genus Streptomyces. This was the original source of many antibiotics, namely streptomycin. Streptomycin was the first antibiotic against tuberculosis....

. Over 500 species of Streptomyces bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 have been described. As with the other Actinobacteria, streptomycetes are gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...

, and have genomes with high guanine and cytosine content
GC-content
In molecular biology and genetics, GC-content is the percentage of nitrogenous bases on a DNA molecule that are either guanine or cytosine . This may refer to a specific fragment of DNA or RNA, or that of the whole genome...

. Found predominantly in soil and decaying vegetation, most streptomycetes produce spore
Spore
In biology, a spore is a reproductive structure that is adapted for dispersal and surviving for extended periods of time in unfavorable conditions. Spores form part of the life cycles of many bacteria, plants, algae, fungi and some protozoa. According to scientist Dr...

s, and are noted for their distinct "earthy" odor that results from production of a volatile metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

, geosmin
Geosmin
Geosmin, which literally translates to "earth smell", is an organic compound with a distinct earthy flavour and aroma, and is responsible for the earthy taste of beets and a contributor to the strong scent that occurs in the air when rain falls after a dry spell of weather or when soil is...

.

Streptomycetes are characterised by a complex secondary metabolism
Secondary metabolism
Secondary metabolism is a term for pathways and small molecule products of metabolism that are not absolutely required for the survival of the organism. Examples of the products include antibiotics and pigments. To distinguish non-secondary metabolism, the term basic metabolism is sometimes used...

. They produce over two-thirds of the clinically useful antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s of natural origin (e.g., neomycin
Neomycin
Neomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951...

, chloramphenicol
Chloramphenicol
Chloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...

). The now uncommonly-used streptomycin
Streptomycin
Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...

 takes its name directly from Streptomyces. Streptomycetes are infrequent pathogens, though infections in human such as mycetoma
Mycetoma
Eumycetoma is a chronic, specific, granulomatous, fungal disease. It mainly affects the foot; and Mycetoma pedis is also known as Madura foot. This infection is endemic in Africa, India, and Central and South America.-Causes and presentation:...

 can be caused by S. somaliensis and S. sudanensis, and in plants can be caused by S. caviscabies and S. scabies.

Selected species

Roughly 550 species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

 of Streptomyces are recognized at present, but new ones are still being discovered (e.g., S. aomiensis and S. hyderabadensis, both described in 2010). Many species are named after their colorful hyphae and/or spore
Spore
In biology, a spore is a reproductive structure that is adapted for dispersal and surviving for extended periods of time in unfavorable conditions. Spores form part of the life cycles of many bacteria, plants, algae, fungi and some protozoa. According to scientist Dr...

s.

Significant Streptomyces species include:

  • Streptomyces achromogenes
    Streptomyces achromogenes
    Streptomyces achromogenes is a species of gram-positive bacterium that belongs in the genus Streptomyces. S. achromogenes can be grown at 28°C in a medium of yeast and malt extract with glucose....

  • Streptomyces alboniger
  • Streptomyces albus
    Streptomyces albus
    Streptomyces albus is a bacterial species from which the pseudodisaccharide aminoglycoside salbostatin was isolated....

  • Streptomyces ambofaciens
  • Streptomyces aomiensis
  • Streptomyces aureomonopodiales
  • Streptomyces aureofaciens
    Streptomyces aureofaciens
    Streptomyces aureofaciens is a species of Streptomyces.It is the source of many tetracycline antibiotics....

  • Streptomyces avermitilis
  • Streptomyces avidinii
  • Streptomyces bikiniensis
  • Streptomyces caespitosus
    Streptomyces caespitosus
    Streptomyces caespitosus is a species of actinobacteria. It produces chemotherapeutic drug mitomycin C....

  • Streptomyces cattleya
  • Streptomyces caviscabies
  • Streptomyces chartreusis
  • Streptomyces chusanensis
  • Streptomyces clavuligerus
    Streptomyces clavuligerus
    Streptomyces clavuligerus is a species of Gram-positive bacterium that produces clavulanic acid.S. clavuligerus ATCC 27064 was first described by Higgens and Kastner, who isolated it from a South American soil sample...

  • Streptomyces coelicolor
    Streptomyces coelicolor
    Streptomyces coelicolor is a soil-dwelling Gram-positive bacterium that belongs to the genus Streptomyces.-Usage in biotechnology:Strains of S. coelicolor produce various antibiotics, including actinorhodin, methylenomycin, undecylprodigiosin, and perimycin. Certain strains of S. coelicolor can...

  • Streptomyces diastaticus
  • Streptomyces exfoliatus
  • Streptomyces faecalis
  • Streptomyces faecium
  • Streptomyces felleus
  • Streptomyces ferralitis

  • Streptomyces fimbriatus
  • Streptomyces filementosus
  • Streptomyces fradiae
    Streptomyces fradiae
    Streptomyces fradiae is a species of actinobacteria. It produces the antibiotics neomycin, tylosin and fosfomycin ....

  • Streptomyces fulvissimus
  • Streptomyces globisporus
    Streptomyces globisporus
    Streptomyces globisporus is a soil-dwelling Gram-positive bacterium. C-1027 is produced by this species, which is one of the most potent antitumor agents....

  • Streptomyces griseoruber
  • Streptomyces griseoviridis
  • Streptomyces griseus
    Streptomyces griseus
    Streptomyces griseus is a member bacterial species of the genus Streptomyces and are commonly found in soil. A few strains have been also reported from deep sea sediments. These are Gram positive bacterium with high GC content. Along with most other streptomycetes S...

  • Streptomyces hyderabadensis
  • Streptomyces hygroscopicus
  • Streptomyces iysosuperficus
  • Streptomyces lactamdurans
  • Streptomyces lavendulae
  • Streptomyces lincolnensis
  • Streptomyces lividans
  • Streptomyces lusitanus
  • Streptomyces mediterranei
  • Streptomyces niveus
  • Streptomyces nodosus
  • Streptomyces noursei
  • Streptomyces novocastria
  • Streptomyces olivochromogenes
  • Streptomyces orientalis
    Streptomyces orientalis
    Streptomyces orientalis is a bacterium. It is considered an Actinobacterium species. Streptomyces orientalis are responsible for sore throat infections and wound infections in humans, and are also a significant cause of morbidity in goat populations....


  • Streptomyces peucetius
  • Streptomyces phaeochromogenes'
  • Streptomyces platensis
  • Streptomyces pulveraceus
  • Streptomyces rimosus
  • Streptomyces roseosporus
    Streptomyces roseosporus
    Streptomyces roseosporus is a species of actinobacteria. It produces the novel antibiotic daptomycin ....

  • Streptomyces sannurensis
  • Streptomyces scabies
  • Streptomyces somaliensis
  • Streptomyces stanford
  • Streptomyces stramineus
  • Streptomyces sudanensis
  • Streptomyces tendae
  • Streptomyces thermodiastaticus
  • Streptomyces thermoviolaceus
  • Streptomyces toxytricini
    Streptomyces toxytricini
    Streptomyces toxytricini is a Gram-positive bacterium belonging to the genus Streptomyces. It produces the pancreatic lipase inhibitor lipstatin, of which the antiobesity drug orlistat is a derivative....

  • Streptomyces tsukubaensis
    Streptomyces tsukubaensis
    Streptomyces tsukubaensis is a species of actinobacteria. It produces the immunosuppressive drug tacrolimus....

  • Streptomyces tubercidicus
  • Streptomyces venezuelae
    Streptomyces venezuelae
    Streptomyces venezuelae is a species of soil-dwelling Gram-positive bacterium of the genus Streptomyces.S. venezuelae is filamentous...

  • Streptomyces verticillus
  • Streptomyces violaceoruber
  • Streptomyces violaceusniger
  • Streptomyces violochromogenes
  • Streptomyces viridochromeogenes

Saccharopolyspora erythraea
Saccharopolyspora erythraea
Saccharopolyspora erythraea, formerly known as Streptomyces erythraeus, is a species of actinomycete bacteria within the genus Saccharopolyspora.Saccharopolyspora erythraea is known for the production of the macrolide antibiotic erythromycin...

 was formerly placed in the present genus too (as Streptomyces erythraeus).

Genomics

The complete genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 of "S. coelicolor" strain A3(2) was published in 2002. At the time, the S. coelicolor genome was thought to contain the largest number of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s of any bacterium. The chromosome is 8,667,507 bp
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

 long with a GC-content of 72.1% and is predicted to contain 7,825 protein encoding genes.
In terms of taxonomy, "S. coelicolor" A3(2) belongs to the species of S. violaceoruber and not a validly described separate species; "S. coelicolor" A3(2) is not to be mistaken for the actual S. coelicolor
Streptomyces coelicolor
Streptomyces coelicolor is a soil-dwelling Gram-positive bacterium that belongs to the genus Streptomyces.-Usage in biotechnology:Strains of S. coelicolor produce various antibiotics, including actinorhodin, methylenomycin, undecylprodigiosin, and perimycin. Certain strains of S. coelicolor can...

 (Müller).

The first complete genome sequence of S. avermitilis was completed in 2003. Each of these genomes forms a chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 with a linear structure, unlike most bacterial genomes, which exist in the form of circular chromosomes. The genome sequence of S. scabies, a member of the genus with the ability to cause potato scab disease, has been determined at the Wellcome Trust Sanger Institute
Sanger Institute
The Wellcome Trust Sanger Institute is a non-profit, British genomics and genetics research institute, primarily funded by the Wellcome Trust....

 and is currently in annotation, with publication scheduled for 2009.

Biotechnology

In recent years, biotechnology
Biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...

 researchers have begun using Streptomyces species for heterologous expression
Heterologous expression
Heterologous expression is to express a gene or part of a gene in a host organism, which does not naturally have this gene or gene fragment.This is mainly done in recombinant DNA technology....

 of proteins. Traditionally, Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

 was the species of choice to express eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 genes since it was well understood and easy to work with. Expression of eukaryotic proteins in E. coli may be problematic however, due to the inability of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 to glycosylate
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

 proteins. And there may also be issues with incorrectly folded proteins
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....

, which may lead to insolubility, deposition in inclusion bodies
Inclusion bodies
Inclusion bodies are nuclear or cytoplasmic aggregates of stainable substances, usually proteins. They typically represent sites of viral multiplication in a bacterium or a eukaryotic cell and usually consist of viral capsid proteins...

, and loss of bioactivity of the product. Though E. coli have secretion mechanisms, these are of low efficiency and result in secretion into the periplasmic space
Periplasmic space
The periplasmic space or periplasm is a space between the peptidoglycan cell wall and inner membrane of Gram-negative bacteria or the equivalent space outside the inner membrane of Gram-positive bacteria. It may constitute up to 40% of the total cell volume in Gram-negative species, and is...

, whereas secretion by a Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...

 bacterium such as a Streptomyces spp. results in secretion directly into the extracellular medium. In addition, Streptomyces spp. have more efficient secretion mechanisms than E.coli. The properties of the secretion system is an advantage for industrial production of heterologously expressed protein because it simplifies subsequent purification steps and may increase yield. These properties among others make Streptomyces spp. an attractive alternative to other bacteria such as E. coli and Bacillus subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...

. As is true for all bacteria, Streptomyces spp. does not have the ability to glycosylate proteins, which may necessitate using an eukaryotic host, if this is required for bioactivity of the product.

Medicine

Streptomyces is the largest antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

-producing genus, producing antibacterial, antifungal
Antifungal drug
An antifungal medication is a medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis , serious systemic infections such as cryptococcal meningitis, and others...

, and anti-parasitic drugs, and also a wide range of other bioactive
Biological activity
In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or pharmacophore but can be modified by the other...

 compounds such as immunosuppressants
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...

.

Antifungals

Streptomycetes produce numerous antifungal compounds of medicinal importance, including nystatin
Nystatin
Nystatin is a polyene antifungal medication to which many molds and yeast infections are sensitive, including Candida. Due to its toxicity profile, there are currently no injectable formulations of this drug on the US market...

 (from S. noursei), amphotericin B
Amphotericin B
Amphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...

 (from S. nodosus), and natamycin
Natamycin
Natamycin , also known as pimaricin, is a naturally occurring antifungal agent produced during fermentation by the bacterium Streptomyces natalensis, commonly found in soil. Natamycin has a very low solubility in water, however, natamycin is effective at very low levels. Most molds have an MIC of...

 (from S. natalensis).

Antibacterials

Members of the Streptomyces genus are the source for numerous antibacterial pharmaceutical agents; among the most important of these are:
  • Cefoxitin
    Cefoxitin
    Cefoxitin is a cephamycin antibiotic developed by Merck & Co., Inc., often grouped with the second−generation cephalosporins. It is sold under the brand name Mefoxin.- Microbiology :...

     (from S. lactamdurans)
  • Chloramphenicol
    Chloramphenicol
    Chloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...

     (from S. venezuelae
    Streptomyces venezuelae
    Streptomyces venezuelae is a species of soil-dwelling Gram-positive bacterium of the genus Streptomyces.S. venezuelae is filamentous...

    )
  • Daptomycin
    Daptomycin
    Daptomycin is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. It is a naturally occurring compound found in the soil saprotroph Streptomyces roseosporus. Its distinct mechanism of action means that it may be useful in treating infections...

     (from S. roseosporus
    Streptomyces roseosporus
    Streptomyces roseosporus is a species of actinobacteria. It produces the novel antibiotic daptomycin ....

    )
  • Fosfomycin
    Fosfomycin
    Fosfomycin is a broad-spectrum antibiotic produced by certain Streptomyces species.-Uses:...

     (from S. fradiae
    Streptomyces fradiae
    Streptomyces fradiae is a species of actinobacteria. It produces the antibiotics neomycin, tylosin and fosfomycin ....

    )
  • Lincomycin
    Lincomycin
    Lincomycin is a lincosamide antibiotic that comes from the actinomyces Streptomyces lincolnensis. It has been structurally modified by thionyl chloride to its more commonly known 7-chloro-7-deoxy derivative, clindamycin...

     (from S. lincolnensis)
  • Neomycin
    Neomycin
    Neomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951...

     (from S. fradiae)
  • Puromycin
    Puromycin
    Puromycin is an antibiotic that is a protein synthesis inhibitor by inhibiting translation.-Inhibition of translation:Puromycin is an aminonucleoside antibiotic, derived from the Streptomyces alboniger bacterium, that causes premature chain termination during translation taking place in the...

     (from S. alboniger)
  • Rifamycin
    Rifamycin
    The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium Amycolatopsis mediterranei or artificially. They are a subclass of the larger family Ansamycin...

     (from S. mediterranei)
  • Streptomycin
    Streptomycin
    Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...

     (from S. griseus
    Streptomyces griseus
    Streptomyces griseus is a member bacterial species of the genus Streptomyces and are commonly found in soil. A few strains have been also reported from deep sea sediments. These are Gram positive bacterium with high GC content. Along with most other streptomycetes S...

    )
  • Tetracycline (from S. rimosus)
  • Vancomycin
    Vancomycin
    Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...

     (from S. orientalis
    Streptomyces orientalis
    Streptomyces orientalis is a bacterium. It is considered an Actinobacterium species. Streptomyces orientalis are responsible for sore throat infections and wound infections in humans, and are also a significant cause of morbidity in goat populations....

    )


Clavulanic acid
Clavulanic acid
Clavulanic acid is a competitive β-lactamase inhibitor combined with penicillin group antibiotics to overcome certain types of antibiotic resistance. It is used to overcome resistance in bacteria that secrete β-lactamase, which otherwise inactivates most penicillins...

 (from S. clavuligerus
Streptomyces clavuligerus
Streptomyces clavuligerus is a species of Gram-positive bacterium that produces clavulanic acid.S. clavuligerus ATCC 27064 was first described by Higgens and Kastner, who isolated it from a South American soil sample...

) is a drug used in combination with some antibiotics (like amoxicillin
Amoxicillin
Amoxicillin , formerly amoxycillin , and abbreviated amox, is a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral...

) in order to block and/or weaken some bacterial resistance-mechanisms by irreversible beta-lacatamase inhibition.

Antiparasitic drugs

S. avermitilis is responsible for the production of one of the most widely employed drugs against nematode and arthropod infestations, ivermectin.

Other

Less commonly, streptomycetes produce compounds used in other medical treatments: migrastatin
Migrastatin
Migrastatin is an organic compound which naturally occurs in the Streptomyces platensis bacteria. Migrastatin and several of its analogues have shown to have potential in treating cancer, as it inhibits the metastasis of cancer cells....

 (from S. platensis) and bleomycin
Bleomycin
Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...

 (from S. verticillus) are antineoplastic (anti-cancer) drugs.

S. hygroscopicus and S. viridochromeogenes produce the natural herbicide bialaphos.

External links

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