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

Streptomyces ''Streptomyces'' is the largest genus of Actinomycetota and the type genus of the family Streptomycetaceae. Over 500 species of ''Streptomyces'' bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, ...

'' 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 bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

-producing genus of

Actinomycetota The ''Actinomycetota'' (or ''Actinobacteria'') are a phylum of all gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture and forests depend on their contributions to soi ...

, 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 crypto ...

, antiparasitic drugs, and

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

. ''Streptomyces'' isolates are typically initiated with the aerial

hyphal A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium. Structure A hypha consists of one or ...

formation from the

mycelium Mycelium (plural mycelia) is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae. Fungal colonies composed of mycelium are found in and on soil and many other substrate (biology), substrates. A typical single ...

Anticancer medicines

''Streptomyces'', yielded the medicines

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used togeth ...

(Doxil),

daunorubicin Daunorubicin, also known as daunomycin, is a chemotherapy medication used to treat cancer. Specifically it is used for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and Kaposi's sarcoma. It ...

(DaunoXome), and

streptozotocin Streptozotocin or streptozocin (INN, USP) (STZ) is a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain canc ...

(Zanosar). Doxorubicin is the precursor to

valrubicin Valrubicin (''N''-trifluoroacetyladriamycin-14-valerate, trade name Valstar) is a chemotherapy drug used to treat bladder cancer. Valrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into ...

(Valstar),

myocet Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used combina ...

, and

pirarubicin Pirarubicin (INN) is an anthracycline drug. An analogue of the anthracycline antineoplastic antibiotic doxorubicin. Pirarubicin intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and p ...

. Daunorubicin is the precursor to

idarubicin Idarubicin or 4-demethoxydaunorubicin is an anthracycline antileukemic drug. It inserts itself into DNA and prevents DNA unwinding by interfering with the enzyme topoisomerase II. It is an analog of daunorubicin, but the absence of a methoxy grou ...

(Idamycin),

epirubicin Epirubicin is an anthracycline drug used for chemotherapy. It can be used in combination with other medications to treat breast cancer in patients who have had surgery to remove the tumor. It is marketed by Pfizer under the trade name Ellence in t ...

(Ellence), and

zorubicin Zorubicin (INN) is an anthracycline Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from ''Streptomyces'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, st ...

. ''Streptomyces'' is the original source of

dactinomycin Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovari ...

(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 , chemical_formula = , C=55 , H=84 , N=1 ...

(Blenoxane),

pingyangmycin Pingyangmycin (also known as bleomycin A5) is an antitumor glycopeptide antibiotic belonging to the bleomycin family, which is produced by ''Streptomyces verticillus'' var.'' pingyangensis n.sp.'', a Subspecies, variety of ''Streptomyces verticil ...

(Bleomycin A₅),

mitomycin C Mitomycin C is a mitomycin that is used as a 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 cancers, and breast c ...

(Mutamycin),

rebeccamycin Rebeccamycin (NSC 655649) is a weak topoisomerase I inhibitor isolated from ''Nocardia sp.'' It is structurally similar to staurosporine, but does not show any inhibitory activity against protein kinases. It shows significant antitumor properties ...

staurosporine Staurosporine (antibiotic AM-2282 or STS) is a natural product originally isolated in 1977 from the bacterium '' Streptomyces staurosporeus''. It was the first of over 50 alkaloids to be isolated with this type of bis-indole chemical structure. Th ...

(precursor to

stauprimide Stauprimide is a semi-synthetic analog of the staurosporine family of indolocarbazoles. Stauprimide was first published in 1994 as part of an extensive structure-activity investigation to improve the selective inhibition of protein kinase C as a p ...

and

midostaurin Midostaurin, sold under the brand name Rydapt & Tauritmo both by Novartis, is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced syste ...

neothramycin Neothramycin A and B Neothramycin A and B are stereoisomeric antibiotics with anticancer activity. The stereoisomers are interchangeable in aqueous solution and the antibiotic, Neothramycin, contains both in approximately equal amounts. They belo ...

aclarubicin Aclarubicin (INN) or aclacinomycin A is an anthracycline drug that is used in the treatment of cancer. Soil bacteria '' Streptomyces galilaeus'' can produce aclarubicin. It can induce histone eviction from chromatin Chromatin is a complex of ...

, tomaymycin,

sibiromycin Sibiromycin is an antitumor antibiotic with the molecular formula C24H33N3O7 which is produced by the bacterium '' Streptosporangium sibiricum''. Sibiromycin is a pyrrolobenzodiazepine Pyrrolobenzodiazepines, (PBD) are a class of compound that m ...

, and mazethramycin. Derivatives of ''Streptomycetes'' isolate

migrastatin Migrastatin is an organic compound which naturally occurs in the '' Streptomyces platensis'' bacteria. Migrastatin and several of its analogues (including Isomigrastatin) have shown to have potential in treating cancer, as it inhibits the metastas ...

, including

isomigrastatin Isomigrastatin is an analogue of migrastatin, an organic compound that naturally occurs in the '' Streptomyces platensis'' bacteria. Isomigrastatin has shown promise as a drug in the treatment of cancer Cancer is a group of diseases invol ...

, dorrigocin A & B, and the synthetic derivative

macroketone Macroketones are macrocyclic compounds that contain a ketone functional group. Macroketones form the central rings systems of some synthetic polyketide antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. ...

, are being researched for anticancer activity.

Antibiotics

Most clinical antibiotics were found during the "golden age of antibiotics" (1940s–1960s).

Actinomycin Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovari ...

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, endocarditis, brucellosis, ''Burkholderia'' infection, plague, tularemia, and rat bite fever. Fo ...

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 Clavulanic acid is a β-lactam drug that functions as a mechanism-based β-lactamase inhibitor. While not effective by itself as an antibiotic, when combined with penicillin-group antibiotics, it can overcome antibiotic resistance in bacteria t ...

(''

Streptomyces clavuligerus ''Streptomyces clavuligerus'' is a species of Gram-positive bacterium notable for producing clavulanic acid. ''S. clavuligerus'' ATCC 27064 (NRRL 3585, DSM 738) was first described by Higgens and Kastner (1971), who isolated it from a South Ame ...

'') is used in combination with some antibiotics (such as

amoxicillin Amoxicillin is an antibiotic medication used to treat a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less c ...

) to weaken bacterial-resistance. Novel anti-infectives being developed include the

guadinomine Guadinomines are anti-infective compounds produced by '' Streptomyces'' sp. K01-0509. Guadinomine B is the most potent known inhibitor of the Type III secretion system (TTSS) of Gram-negative bacteria. The guadinomine (gdn) biosynthetic gene cluste ...

s (from ''Streptomyces'' sp. K01-0509), inhibitors of the

type III secretion system The type III secretion system (T3SS or TTSS), also called the injectisome, is one of the bacterial secretion systems used by bacteria to secrete their effector proteins into the host's cells to promote virulence and colonisation. The T3SS is a ...

. Non-''Streptomyces''

actinomycetes The Actinomycetales is an order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally gram-positive and anaerobic and have mycelia in a filamentous and branching growth pattern. Some actinomycete ...

, filamentous

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

, and non-filamentous

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

, have also yielded important antibiotics.

Antifungals

Nystatin Nystatin, sold under the brandname Mycostatin among others, is an antifungal medication. It is used to treat '' Candida'' infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be ...

(''

Streptomyces noursei ''Streptomyces noursei'' is a bacterium species in the genus '' Streptomyces''. Uses Nystatin Nystatin, sold under the brandname Mycostatin among others, is an antifungal medication. It is used to treat '' Candida'' infections of the skin inc ...

''),

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 cryptococcosis. Fo ...

(''

Streptomyces nodosus ''Streptomyces nodosus'' is a bacterial species in the genus ''Streptomyces''. Uses ''Streptomyces nodosus'' is used to produce amphotericin B. Saquayamycins ( saquayamycins A, B, C and D) are antibiotics of the aquayamycin Aquayamycin ...

''), ossamycin (''

Streptomyces hygroscopicus ''Streptomyces hygroscopicus'' is a bacterial species in the genus '' Streptomyces''. It was first described by Hans Laurits Jensen in 1931. Biochemistry Cultures of different strains of ''S. hygroscopicus'' can be used to produce a number of ...

''), 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 industr ...

(''

Streptomyces natalensis ''Streptomyces natalensis'' is a bacterial species in the genus ''Streptomyces''. Uses Natamycin Natamycin, also known as pimaricin, is an antifungal medication used to treat fungal infections around the eye. This includes infections of ...

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

Immunosuppressants

Sirolimus Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, ...

(Rapamycin),

ascomycin Ascomycin, also called Immunomycin, FR-900520, FK520, is an ethyl analog of tacrolimus (FK506) with strong immunosuppressant properties. It has been researched for the treatment of autoimmune diseases and skin diseases, and to prevent rejection ...

, and

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

were isolated from ''Streptomyces''.

Pimecrolimus Pimecrolimus is an immunomodulating agent of the calcineurin inhibitor class used in the treatment of atopic dermatitis (eczema). It is available as a topical cream, once marketed by Novartis (however, Galderma has been promoting the compound in ...

is a derivative of ascomycin.

Ubenimex Ubenimex (INN), also known more commonly as bestatin, is a competitive, reversible protease inhibitor. It is an inhibitor of arginyl aminopeptidase (aminopeptidase B), leukotriene A4 hydrolase (a zinc metalloprotease that displays both epoxide ...

is derived from ''S. olivoreticuli''.

Antiparasitics

Streptomyces avermitilis ''Streptomyces avermitilis'' is a species of bacteria in the genus ''Streptomyces''. This bacterium was discovered by Satoshi Ōmura in Shizuoka Prefecture, Japan. The first complete genome sequence of ''S. avermitilis'' was completed in 2003. T ...

'' synthesizes the antiparasitic

ivermectin Ivermectin (, '' EYE-vər-MEK-tin'') 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, today it is used to treat inf ...

(Stromectol). Other antiparasitics made by ''Streptomyces'' include,

milbemycin oxime Milbemycin oxime, sold under the brand name Interceptor among others, is a veterinary medication from the group of milbemycins, used as a broad spectrum antiparasitic. It is active against worms (anthelmintic) and mites (miticide). Mechanism of a ...

moxidectin Moxidectin is an anthelmintic drug used in animals to prevent or control parasitic worms (helminths), such as heartworm and intestinal worms, in dogs, cats, horses, cattle and sheep. Moxidectin kills some of the most common internal and external ...

, and

milbemycin The milbemycins are a group of macrolides chemically related to the avermectins and were first isolated in 1972 from '' Streptomyces hygroscopicus''. They are used in veterinary medicine as antiparasitic agents against worms, ticks and fleas.

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. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'' is the choice bacterium to express

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

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 ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

, the

artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to ''Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her dis ...

precursor artemisinic acid, and

filgrastim Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count. Low neutrophil counts may occur with HIV/AIDS, following chemotherapy or radiation poisoning, or be of an unknown cause. It may ...

(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 ''Bacillu ...

''. ''

Streptomyces coelicolor ''Streptomyces albidoflavus'' is a bacterium species from the genus of ''Streptomyces'' which has been isolated from soil from Poland. ''Streptomyces albidoflavus'' produces dibutyl phthalate and streptothricins. Small noncoding RNA Bacteri ...

'', ''

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 s ...

'', and ''

Saccharopolyspora erythraea ''Saccharopolyspora erythraea'' is a species of actinomycete bacteria within the genus '' Saccharopolyspora''. ''Saccharopolyspora erythraea'' produces the macrolide antibiotic erythromycin. Cytochrome P450 Cytochromes P450 (CYPs) are a sup ...

'', are capable of secondary metabolite production. ''

'' 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 techno ...

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. ''

'' and '' Streptomyces viridochromeogenes'' produce the herbicide

bialaphos Bialaphos is a natural herbicide produced by the bacteria ''Streptomyces hygroscopicus'' and ''Streptomyces viridochromogenes''. Bialaphos is a protoxin and nontoxic as is. When it is metabolized by the plant, the glutamic acid analog glufosinate ...

. Expansion of ''Streptomyces'' screenings have included

endophytes An endophyte is an endosymbiont, often a bacterium or fungus, that lives within a plant for at least part of its life cycle without causing apparent disease. Endophytes are ubiquitous and have been found in all species of plants studied to date; h ...

extremophiles An extremophile (from Latin ' meaning "extreme" and Greek ' () meaning "love") is an organism that is able to live (or in some cases thrive) in extreme environments, i.e. environments that make survival challenging such as due to extreme temper ...

, and

marine Marine is an adjective meaning of or pertaining to the sea or ocean. Marine or marines may refer to: Ocean * Maritime (disambiguation) * Marine art * Marine biology * Marine debris * Marine habitats * Marine life * Marine pollution Military * ...

varieties. A recent screening of TCM extracts revealed a ''Streptomyces'' that produces a number of antitubercular pluramycins.Wailupemycins are bio-active

pyrone Pyrones or pyranones are a class of heterocyclic chemical compounds. They contain an unsaturated six-membered ring containing one oxygen atom and a ketone functional group. There are two isomers denoted as 2-pyrone and 4-pyrone. The 2-pyrone (or ...

s isolated from marine ''

''. Mayamycin has been shown to have

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

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, fern ...

References

{{reflist, 2

External links

StreptomeDB

Antibiotics and Streptomyces : the future of antibiotic discovery

Bioprospecting for Microbial Endophytes and Their Natural Products - 2003

isolates {{About, , the linguistics term dealing with languages unrelated to any other language in the world, Language isolate, other uses, Isolate (disambiguation){{!Isolate Isolates is a term used in developmental psychology and family studies, to describ ...

Pharmaceutical isolates Chemotherapy Cancer Antibiotics Immunosuppressants Antifungals Antiparasitic agents

Anticancer medicines

Antibiotics

Antifungals

Immunosuppressants

Antiparasitics

Biotechnology

Other

See also

References

External links