''Streptomyces'' isolates have yielded the majority of human, animal, and agricultural antibiotics, as well as a number of fundamental chemotherapy medicines. ''

Streptomyces ''Streptomyces'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...

'' is the largest

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

-producing genus of

Actinomycetota The Actinomycetota (or Actinobacteria) are a diverse phylum of Gram-positive bacteria with high GC content. They can be terrestrial or aquatic. They are of great importance to land flora because of their contributions to soil systems. In soil t ...

, producing chemotherapy, antibacterial,

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...

, antiparasitic drugs, and

immunosuppressants Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...

. ''Streptomyces'' isolates are typically initiated with the aerial hyphal formation from the

mycelium Mycelium (: mycelia) is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae. Its normal form is that of branched, slender, entangled, anastomosing, hyaline threads. Fungal colonies composed of mycelium are fo ...

Anticancer medicines

''Streptomyces'', yielded the medicines doxorubicin (Doxil), daunorubicin (DaunoXome), and streptozotocin (Zanosar). Doxorubicin is the precursor to valrubicin (Valstar), myocet, and pirarubicin. Daunorubicin is the precursor to idarubicin (Idamycin), epirubicin (Ellence), and zorubicin. ''Streptomyces'' is the original source of dactinomycin (Cosmegen),

bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , C=55 , H=84 , N=17 , O=21 , S=3 , SMI ...

(Blenoxane), pingyangmycin (Bleomycin A₅),

mitomycin C Mitomycin C is a mitomycin that is used as a chemotherapy, chemotherapeutic agent by virtue of its antitumour activity. Medical uses It is given intravenously to treat upper gastro-intestinal cancers (e.g. esophageal carcinoma), anal cancer ...

(Mutamycin), rebeccamycin, staurosporine (precursor to stauprimide and midostaurin), neothramycin, aclarubicin, tomaymycin, sibiromycin, and mazethramycin. Derivatives of ''Streptomycetes'' isolate migrastatin, including isomigrastatin, dorrigocin A & B, and the synthetic derivative macroketone, are being researched for anticancer activity.

Antibiotics

Most clinical antibiotics were found during the "golden age of antibiotics" (1940s–1960s). Actinomycin was the first antibiotic isolated from ''Streptomyces'' in 1940, followed by

streptomycin Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, Mycobacterium avium complex, ''Mycobacterium avium'' complex, endocarditis, brucellosis, Burkholderia infection, ''Burkholderia'' i ...

three years later. Antibiotics from ''Streptomyces'' isolates (including various

aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...

s) would go on to comprise over two-thirds of all marketed antibiotics. ''Streptomyces''-derived antibiotics include: Clavulanic acid ('' Streptomyces clavuligerus'') is used in combination with some antibiotics (such as amoxicillin) to weaken bacterial-resistance. Novel anti-infectives being developed include the guadinomines (from ''Streptomyces'' sp. K01-0509), inhibitors of the type III secretion system. Non-''Streptomyces''

actinomycetes The Actinomycetales is an Scientific classification, order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally Gram-positive bacteria, gram-positive and anaerobic and have mycelia in a filamento ...

, filamentous

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

, and non-filamentous

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

, have also yielded important antibiotics.

Antifungals

Nystatin Nystatin, sold under the brand name Mycostatin among others, is an antifungal medication. It is used to treat ''Candida (fungus), Candida'' infections of the skin including diaper rash, Candidiasis, thrush, esophageal candidiasis, and vaginal ...

('' Streptomyces noursei''),

amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococ ...

('' Streptomyces nodosus''), ossamycin ('' Streptomyces hygroscopicus''), and

natamycin Natamycin, also known as pimaricin, is an antifungal medication used to treat fungal infections around the eye. This includes infections of the eyelids, conjunctiva, and cornea. It is used as eyedrops. Natamycin is also used in the food in ...

(''

Streptomyces natalensis ''Streptomyces natalensis'' is a bacterial species in the genus '' Streptomyces''. Uses Natamycin is an antifungal agent produced during fermentation by ''S. natalensis''. References Further reading * * External links natalensis< ...

'') are antifungals isolated from ''Streptomyces''.

Immunosuppressants

Sirolimus (Rapamycin), ascomycin, and

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...

were isolated from ''Streptomyces''. Pimecrolimus is a derivative of ascomycin. Ubenimex is derived from ''S. olivoreticuli''.

Antiparasitics

'' Streptomyces avermitilis'' synthesizes the antiparasitic

ivermectin Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, it is used to treat infestations including head lice ...

(Stromectol). Other antiparasitics made by ''Streptomyces'' include, milbemycin oxime, moxidectin, and milbemycin.

Biotechnology

Domain_organization_of_PKS_of_rapamycin_and_biosynthetic_intermediates

Traditionally, ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' is the choice bacterium to express

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

and recombinant genes. ''E. coli'' is well understood and has a successful track record producing

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

, the artemisinin precursor artemisinic acid, and filgrastim (Neupogen). However, use of ''E. coli'' has limitations including misfolding of eukaryotic proteins, insolubility issues, deposition in inclusion bodies, low secretion efficiency, secretion to periplasmic space. ''Streptomyces'' offers potential advantages including superior secretion mechanisms, higher yields, a simpler end-product purification process, making ''Streptomyces'' an attractive alternative to ''E. coli'' and ''

Bacillus subtilis ''Bacillus subtilis'' (), known also as the hay bacillus or grass bacillus, is a gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacill ...

''. '' Streptomyces coelicolor'', '' Streptomyces avermitilis'', ''

Streptomyces griseus ''Streptomyces griseus'' is a species of bacteria in the genus '' Streptomyces'' commonly found in soil. A few strains have been also reported from deep-sea sediments. It is a Gram-positive bacterium with high GC content. Along with most other ...

'', and '' Saccharopolyspora erythraea'', are capable of secondary metabolite production. '' Streptomyces coelicolor'' has shown useful for the

heterologous expression Heterologous expression refers to the expression of a gene or part of a gene in a host organism that does not naturally have the gene or gene fragment in question. Insertion of the gene in the heterologous host is performed by recombinant DNA te ...

of proteins. Methods like "ribosome engineering" have been used to achieve 180-fold higher yields with ''S. coelicolor''.

Other

StreptomeDB, a directory of ''Streptomyces'' isolates, contains over 2400 compounds isolated from more than 1900 strains. '' Streptomyces hygroscopicus'' and '' Streptomyces viridochromeogenes'' produce the herbicide bialaphos. Expansion of ''Streptomyces'' screenings have included endophytes,

extremophiles An extremophile () is an organism that is able to live (or in some cases thrive) in extreme environments, i.e., environments with conditions approaching or stretching the limits of what known life can adapt to, such as extreme temperature, pres ...

, and marine varieties. A recent screening of TCM extracts revealed a ''Streptomyces'' that produces a number of antitubercular pluramycins. Wailupemycins are bio-active pyrones isolated from marine ''

''. Mayamycin has been shown to have

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

properties. Germicidin are a group of four compounds that act as autoregulatory inhibitors of

spore germination Germination is the process by which an organism grows from a seed or spore. The term is applied to the sprouting of a seedling from a seed of an angiosperm or gymnosperm, the growth of a sporeling from a spore, such as the spores of fungi, fe ...

References

{{reflist, 2

External links

StreptomeDB

Antibiotics and Streptomyces : the future of antibiotic discovery

Bioprospecting for Microbial Endophytes and Their Natural Products - 2003

isolates Isolates is a term used in developmental psychology and family studies to describe members of a study group, usually children through young adults, who do not actively participate in cliques or friendship groups. Isolates are one of four types of ...

Pharmaceutical isolates Chemotherapy Cancer Antibiotics Immunosuppressants Antifungals Antiparasitic agents