**2. Bioactivity of** *Streptomyces*

*Streptomyces* produce 70–80% of the natural bioactive substances known for their pharmaceutical or agrochemical applications [9, 10]. Continuously new metabolites with different biological activities are isolated from *Streptomyces* strains [11–14]. The first and most important product of *Streptomyces* is antibiotics [15]. From 1955 the genus *Streptomyces* has been the major supplier of new antibiotics [16]. They are the source of antibacterial, antifungal, antitumor, antiparasitic [17–19], antiviral, insecticide, pesticide, and herbicide substances, in addition to pharmacological substances such as immunomodulators (immunosuppressive and immunostimulatory agents), vasoactive substances, and neurological agents [20].

Enzymes are the most important products of *Streptomyces* after antibiotics [21], such as proteases, lipases, cellulases, amylases, pectinases, and xylanases [22, 23].

#### **2.1. Production of antibiotics by** *Streptomyces*

#### *2.1.1. General*

Antibiotics are produced by a wide range of fungal microorganisms and bacteria, and inhibit or kill other microorganisms at low concentrations [24]. A large number of antibiotics have been identified in natural environments, but less than 1% are medically useful. Many antibiotics have been structurally modified in the laboratory to increase their effectiveness, forming the class of semisynthetic antibiotics [25].

The history of antibiotics began with the discovery of penicillin by Fleming in the 1940s. The antimicrobial activities of antibiotics produced by microorganisms have been extensively studied, and the research undertaken has allowed completion of the antibacterial arsenal available to doctors and the general public.

Microorganisms producing chloramphenicol, neomycin, tetracycline, and terramycin were isolated in 1953. The discovery of chemotherapeutic agents and the development of new, more powerful drugs revolutionized medicine and have greatly reduced human suffering [26]. It is very well known that the genus *Streptomyces* produces the majority of antibiotics and biologically active secondary metabolites. Nearly 50% of the species *Streptomyces*

isolated are recognized as producers of antibiotics [25]. Actinomycetes synthesize two-thirds of the microbial antibiotics of which about 80% are isolated from the genus *Streptomyces*. Even if other secondary metabolites are included, the actinomycetes remain the largest suppliers with about 60% (*Streptomyces* always have the biggest part with 80%). More than 60 substances with antibiotic activity produced by *Streptomyces* species are used not only in the world of veterinary and human medicine, but also in the field of agriculture and industry. The capacity of the members of the genus *Streptomyces* [27, 28] to produce commercially significant compounds, especially antibiotics, remains unsurpassed, possibly because of the extra-large DNA complement of these bacteria [17]. Antibiotics that come from Actinobacteria are grouped together so that they belong in their major structural classes. Examples of these are ansamycins (ritamycin), macrolides (erythromycin, azithromycin, and clarithromycin), aminoglycosides (streptomycin, kanamycin, tobramycin, gentamicin, and neomycin), tetracyclines, anthracyclines (doxorubicin), and β-lactam (penicillin, cephalosporin, carbapenems, and monobactams). Streptomycin and its varying species strains have been responsible for the production of most antibiotics and it appears that these organisms produce antibiotics to kill off potential competitors [29]. Streptomycin was one of the first antibiotics found. It is produced by *S. griseus* [30]. Today, various *Streptomyces* species are responsible for approximately 75% of both medical and commercial antibiotics and work very well in these areas. Due to the need for new antibiotics, studies have steered towards the isolation of streptomycetes and the careful screening of different habitats in which they are used. It has also been found through research that different conditions such as nutrients, culturing, and other factors may affect how *Streptomyces* develop to form antibiotics. With this in mind the medium constitution along with metabolic capacity of any organism production can affect antibiotic biosynthesis. Research into actinomycetes has found that they are capable of producing more one antibiotic (e.g. *S. griseus and S. hygroscopicus*) and also the same antibiotic can produce various species of Actinobacteria (e.g. streptothricin and actinomycin). Therefore, an antibiotic may be exactly the same with the same chemical composition and antibiotic spectrum as a produced Actinobacterium (**Table 1**). The table gives a list of antibiotics produced by variations of Actinobacteria and how the antimicrobial application has had a profound impact on the medical world where previously cancers, tumors, and even malaria could not be treated.

#### **2.2. Production of enzymes**

metabolites: they are synthesized by simple translation of mRNAs into peptides by ribosomes. NRPSs are enzymes capable of condensing amino acids to form peptides without going through the ribosomal synthesis pathway. PKSs are enzymes capable of synthesizing a particular family of secondary metabolites: polyketides. The enzymes necessary for the synthesis of these polyketides are homologous to fatty acid synthase (FAS), which is responsible for the synthesis of fatty acid chains. Like the FASs these enzymes can couple precursors to form a chain. This chain will then undergo eight post-PKS changes before becoming active. Regarding the carbohydrate (known scientifically as oligosaccharide) route, it is based on the use of enzymes capable of coupling different sugars to form a carbohydrate precursor; this

*Streptomyces* produce 70–80% of the natural bioactive substances known for their pharmaceutical or agrochemical applications [9, 10]. Continuously new metabolites with different biological activities are isolated from *Streptomyces* strains [11–14]. The first and most important product of *Streptomyces* is antibiotics [15]. From 1955 the genus *Streptomyces* has been the major supplier of new antibiotics [16]. They are the source of antibacterial, antifungal, antitumor, antiparasitic [17–19], antiviral, insecticide, pesticide, and herbicide substances, in addition to pharmacological substances such as immunomodulators (immunosuppressive

and immunostimulatory agents), vasoactive substances, and neurological agents [20].

ases, lipases, cellulases, amylases, pectinases, and xylanases [22, 23].

**2.1. Production of antibiotics by** *Streptomyces*

the class of semisynthetic antibiotics [25].

available to doctors and the general public.

*2.1.1. General*

Enzymes are the most important products of *Streptomyces* after antibiotics [21], such as prote-

Antibiotics are produced by a wide range of fungal microorganisms and bacteria, and inhibit or kill other microorganisms at low concentrations [24]. A large number of antibiotics have been identified in natural environments, but less than 1% are medically useful. Many antibiotics have been structurally modified in the laboratory to increase their effectiveness, forming

The history of antibiotics began with the discovery of penicillin by Fleming in the 1940s. The antimicrobial activities of antibiotics produced by microorganisms have been extensively studied, and the research undertaken has allowed completion of the antibacterial arsenal

Microorganisms producing chloramphenicol, neomycin, tetracycline, and terramycin were isolated in 1953. The discovery of chemotherapeutic agents and the development of new, more powerful drugs revolutionized medicine and have greatly reduced human suffering [26]. It is very well known that the genus *Streptomyces* produces the majority of antibiotics and biologically active secondary metabolites. Nearly 50% of the species *Streptomyces*

chain will then undergo modifications that will make the precursor active [8].

**2. Bioactivity of** *Streptomyces*

102 Basic Biology and Applications of Actinobacteria

Research has reported that there are a great variety of enzymes that can be applied to biomicrobial fields and biotechnological industries from different genera of actinomycetes. Using the information available from genome and protein sequencing data, actinomycetes are constantly screened and used for producing amylases, xylanases, proteases, chitinases, cellulases, and other enzymes. Industrial applications, for example, the pronase of *S. griseus* and the kerase of *Streptomyces fradiae*, are used for the commercial production of biotechnology products such as hydrolysate proteins from different protein sources [31]. The proteases of *Streptomyces* have the advantage of easy elimination of the mycelium by filtration or simple centrifugation [32]. Similarly, Actinobacteria have been revealed to be an excellent resource for L-asparginase, which is produced by a range of Actinobacteria, mainly those from soils such as *S. griseus*, *Streptomyces karnatakensis, Streptomyces albidoflavus*, and *Nocardia* spp. [33, 34] (**Table 2**).


**Antibiotic compound** *Streptomyces* **species Application** Sesquiterpene *Streptomyces* sp. Unknown

Streptokordin *Streptomyces* sp. Antitumor Streptomycin *S. griseus* Antimicrobial Streptozotocin *S. achromogenes* Diabetogenic

*rimosus*

Tirandamycins *Streptomyces* sp. Antibacterial

**Table 1.** List of antibiotics produced by different Actinobacteria and their applications.

Aminoacylase Pharmaceuticals Production of semisynthetic

Tetracyclines *Streptomyces achromogenes*; *S.* 

Staurosporinone *Streptomyces* sp. Antitumor; phycotoxicity

Valinomycin *S. griseus* Ionophor; toxic for prokarotes, eukaryotes

**Enzyme Industry Use** *Streptomyces* **strains**

Amylase Detergent Removal of stains *Streptomyces* sp.

Starch Production of glucose,

Cellulase Detergent Removal of stains *S. thermobifida*,

Chitinase Bioremediation Utilization of chitin waste *S. griseus*

Glucose oxidase Baking Strengthening of dough *S. coelicolor*

Laccase Bleaching Clarification (juice), flavor

L-Asparaginase Medicine The treatment of acute

Keratinase

Textile Removal of starch from woven fabrics

Textile Denim finishing, softening of cotton

Paper and pulp Deinking, modification of fibers

Paper and pulp Deinking

penicillins and celpholosorin

Baking Softening of bread; volume *S. erumpons*

fructose, syrups

Drainage improvement

(beer), cork stopper treatment

lymphoblastic leukemia

Antimicrobial

*S. olivaceus S. roseiscleroticus S. sparsogenes*

*Streptomyces* Secondary Metabolites http://dx.doi.org/10.5772/intechopen.79890 105

*halotolerans*, *S.*

*S. antibioctius*

*S. brahimensis*

*S. karnatakensis S. halstedii*

*thermomonospora*, *S. ruber*


**Table 1.** List of antibiotics produced by different Actinobacteria and their applications.

**Antibiotic compound** *Streptomyces* **species Application**

Anthracyclines *S. galileus* Antitumor

Avermectin *S. avermitilis* Antiparasitic

Bisanthraquinone *Streptomyces* sp. Antibacterial

Chinikomycin *Streptomyces* sp. Anticancer

Chromomycin B, A2, A3 *S. coelicolor* Antitumor

Elaiomycins B and C *Streptomyces* sp. BK 190 Antitumor Frigocyclinone *S. griseus* Antibacterial Glaciapyrroles *Streptomyces* sp. Antibacterial

Lajollamycin *S. nodosus* Antibacterial

Pacificanones A and B *S. pacifica* Antibacterial Piericidins *Streptomyces* sp. Antitumor

Pristinamycine *S. pristinaespiralis* Antibacterial

Salinispyrone *S. pacifica* Unknown Salinispyrone A and B *S. pacifica* Mild cytotoxicity Salinosporamide A *Salinispora tropica* Anticancer; antimalarial

Salinosporamide B and C *S. tropica* Cytotoxicity

Proximicins *Verrucosispora* sp. Antibacterial; anticancer

Rapamycin *S. hygroscopicus* Immunosuppressive; antifungal Resistoflavin methyl ether *Streptomyces* sp. Antibacterial; antioxidative Saliniketal *S. arenicola* Cancer; chemoprevention

Arenimycin *S. arenicola* Antibacterial; anticancer

Carboxamycin *Streptomyces* sp. Antibacterial; anticancer

Daryamides *Streptomyces* sp. Antifungal; anticancer

Chloramphenicol *S. venezuelae* Antibacterial; inhibitor of protein

Hygromycin *S. hygroscopicus* Antimicrobial; immunosuppressive

Lincomycin *S. lincolnensis* Antibacterial; inhibitor of protein

Mitomycin C *S. lavendulae* Antitumor; binds to double-stranded DNA

*Streptomyces* sp. RAUACT-1 Antibacterial

*Streptomyces* sp. Antitumor

disinfectant

and animal cells

biosynthesis

biosynthesis

2-Allyloxyphenol *Streptomyces* sp. Antimicrobial; food preservative; oral

Bafilomycin *S. griseus*, *S. halstedii* ATPase; inhibitor of microorganisms, plant

1,4-Dihydroxy-2-(3-hydroxybutyl)- 9,10-anthraquinone 9,10 anthrac

104 Basic Biology and Applications of Actinobacteria

1,8-Dihydroxy-2-ethyl-3 methylanthraquinone



activity was found to be an effective microorganism against biofilms resulting from *Vibrio* spp., suggesting therefore the potential preventive effect of Actinobacteria against *Vibrio* deseases [35]. Moreover, Latha [36] identified 18 Actinobacteria with probiotic properties isolated from chicken, and their results support the potential preventive effect of *Streptomyces* sp. JD9 as

**Table 3.** Exemles of herbicides produced by actinobacteria used against unwanted herbs and weeds.

**Bioherbicides Biocontrol** *Streptomyces* **strains**

as barnyardness and common crabgrass and broad-

Control of several weeds *S. hygroscopicus*

Monocotyledonous and dicotyledonous weed *S. saganonensis*

Control of several weeds *Streptomyces* sp.

*Streptomyces* sp.

*Streptomyces* Secondary Metabolites http://dx.doi.org/10.5772/intechopen.79890 107

*S. viridochromogenes*

Anisomycin Inhibitor of growth of annual grassy weeds such

Bialaphos Control of annual and perennial grassy weeds and broad-leaved weeds

leaved weeds

The production of pheromone is considered to have important criteria: it is used as a defense against predators, in mate selection, and to conquer host-habitats through mass attack. Sex pheromone peptides in culture supernantrants were mainly found to support aggregation together by the same related species [37, 38]. A good example for aggregative peptide pheromones is *Streptomyces werraensis* LD22, which secretes a heat-stable, acidic pH resistant, low molecular weight peptide pheromone that promotes aggregation propensity and enhances

Microbially derived compounds that share hydrophilic and hydrophobic moieties are surface active biosurfactants that are independent of mineral oil as a feedstock compared with chemi-

Biosurfactants are widely used in scientific research topics (nutrients, cosmetics, textiles, varnishes, pharmaceuticals, mining, and oil recovery) [39, 40]. The lipopeptide antibiotic daptomycin has received great interest as a treatment for Gram-positive bacterial infections; it is marketed as Cubicin by Cubist Pharmaceuticals. Various biosurfactant drugs or bioemulsifiers have been described as a class of Actinobacteria. The best described biosurfactants include a class of glucose-based glycolipids, most of which have a hydrophilic backbone, including

probiotic agents against deseases.

Carbocyclic coformycin and

Phthoxazolin, hydantocidin, and homoalanosin

hydantocidin

Herbicidines and herbimycins

**2.6. Biosurfactants**

cally derived surfactants.

**2.5. Aggregative peptide pheromones**

the biofilm-forming ability of other Actinobacterial isolates.

glycosides associated with glucose units forming a trehalose moiety.

**Table 2.** List of enzymes produced by various Actinobacteria and their industrial application.

#### **2.3. Bioherbicides**

Secondary metabolites of Actinobacteria are used as herbicides against unwanted herbs and weeds (**Table 3**).

#### **2.4. Probiotics**

The use of *Streptomyces* sp. on the growth of tiger shrimp has been previously documented. Also, it was found that antibiotic product extracted from marine Actinobacteria and supplemented in feed was efficient in exhibiting the in vivo effect on feed and the detection of the efficient effect of in vivo white spot syndrome virus in black tiger shrimp. The murine actinomycete


**Table 3.** Exemles of herbicides produced by actinobacteria used against unwanted herbs and weeds.

activity was found to be an effective microorganism against biofilms resulting from *Vibrio* spp., suggesting therefore the potential preventive effect of Actinobacteria against *Vibrio* deseases [35]. Moreover, Latha [36] identified 18 Actinobacteria with probiotic properties isolated from chicken, and their results support the potential preventive effect of *Streptomyces* sp. JD9 as probiotic agents against deseases.

#### **2.5. Aggregative peptide pheromones**

The production of pheromone is considered to have important criteria: it is used as a defense against predators, in mate selection, and to conquer host-habitats through mass attack. Sex pheromone peptides in culture supernantrants were mainly found to support aggregation together by the same related species [37, 38]. A good example for aggregative peptide pheromones is *Streptomyces werraensis* LD22, which secretes a heat-stable, acidic pH resistant, low molecular weight peptide pheromone that promotes aggregation propensity and enhances the biofilm-forming ability of other Actinobacterial isolates.

#### **2.6. Biosurfactants**

**Enzyme Industry Use** *Streptomyces* **strains**

6-aminopenicillanic acid on an

Brewing Clarification; low calorie beer *thermoviolaceus*, *Streptomyces*

Structural determination of the carbohydrate moiety of several

glycoproteins

Secondary metabolites of Actinobacteria are used as herbicides against unwanted herbs and

The use of *Streptomyces* sp. on the growth of tiger shrimp has been previously documented. Also, it was found that antibiotic product extracted from marine Actinobacteria and supplemented in feed was efficient in exhibiting the in vivo effect on feed and the detection of the efficient effect of in vivo white spot syndrome virus in black tiger shrimp. The murine actinomycete

*Streptomyces* sp.

*S. rimosus*

sp.

*S. griseus*

industrial scale

oxytetracycline

Phytase Animal feed Phytate digestibility *S. luteogriseus* R10 Protease Food Cheese making *S. pactum*, *S.*

Medicine Treatment of blood clot Tyrosinase Pharmacy L-Dopa synthesis *S. cyaneofuscatus* Xylanase Baking Conditioning of dough *Streptomyces* spp.

Leather Dehiding

Animal feed Digestibility Paper and pulp Bleach boosting

**Table 2.** List of enzymes produced by various Actinobacteria and their industrial application.

Studying their biochemical functions

Lipase Detergent Removal of stains *S. griseus* Baking Stability of dough Dairy Cheese flavoring Textile Deinking, cleaning *N*-Acetylmuramidase Bacteriology Bacteriostatic enzymes *S. globisporus* Neuraminidase Medical research Cell surface and clinical studies *Streptomyces* sp. Pectinase Beverage Clarification, mashing *S. lydicus* Textile Scouring

Penicillin amidase Commercial significance Production of

106 Basic Biology and Applications of Actinobacteria

β-*N*-Acetyl-Dglucosaminidase

**2.3. Bioherbicides**

weeds (**Table 3**).

**2.4. Probiotics**

Peptide hydrolase Pharmaceuticals Industrial biosynthesis of

Microbially derived compounds that share hydrophilic and hydrophobic moieties are surface active biosurfactants that are independent of mineral oil as a feedstock compared with chemically derived surfactants.

Biosurfactants are widely used in scientific research topics (nutrients, cosmetics, textiles, varnishes, pharmaceuticals, mining, and oil recovery) [39, 40]. The lipopeptide antibiotic daptomycin has received great interest as a treatment for Gram-positive bacterial infections; it is marketed as Cubicin by Cubist Pharmaceuticals. Various biosurfactant drugs or bioemulsifiers have been described as a class of Actinobacteria. The best described biosurfactants include a class of glucose-based glycolipids, most of which have a hydrophilic backbone, including glycosides associated with glucose units forming a trehalose moiety.

#### **2.7. Vitamins**

Vitamin B12 or cobalamine can be synthesized through the fermentation of Actinobacteria [41, 42], and has aroused considerable interest in the possible production of vitamins through microbial fermentation. In addition, cobalt salts in media act as a general Actinobacteria precursor in producing vitamins. Because cobalt is a rather effective bactericidal agent, this precursor must be added carefully. The fermentations producing the antibiotics streptomycin, aureomycin, grisein, and neomycin produce vitamin B12 as well if the medium is supplemented with cobalt without affecting the yields of antibiotic substances.

**2.10. Bioremediation**

*hygroscopicus*, *S. rochei*

**2.11. Control of plant diseases**

**2.12. Nematode control**

**2.13. Enhancement of plant growth**

could be in bioremediation to reduce oil contaminants.

*Streptomyces* **strains Nanoparticles**

*Streptomyces* sp. Zinc, copper, manganese

*S. aureofaciens*, *S. glaucus*, *S. viridogens*, *S. hygroscopicus* Gold

**Table 5.** Exemples of nanoparticules produced by some streptomyces species.

*Streptomyces* sp. GRD, *Streptomyces* sp., *S. albidoflavus*, *S.* 

*Streptomyces* have an important role in the recycling of organic carbon and are able to degrade complex polymers [43]. As reported, the wide use of petroleum hydrocarbons as chemical compounds and fuel in everyday life was considered well-known pollutants of large soil surfaces, causing serious environmental damage. Some studies proved the possible beneficial role of *Streptomyces* flora in the degradation of hydrocarbons [44, 45]. Many Actinobacterial strains are able to solubilize lignin and break down lignin-related compounds following the production of cellulose and hemicellulose-degrading enzymes and extracellular peroxidase [46]. Actinobacteria species are able to grow and live in oil-rich environments, and thus they

Silver

*Streptomyces* Secondary Metabolites http://dx.doi.org/10.5772/intechopen.79890 109

Results of new approaches to control plant diseases. Actinobacteria are potentially used in the agro-industry as a source of agroactive compounds of plant growth (rhizobacteria (polyglycerol polyricinoleate, PGPR) promoting) and for biocontrol [47, 48]. Approximately 60% of the new insecticides and herbicides derived from *Streptomyces* were discovered in the last 5 years*.* Kasugamycin, a bactericidal and fungicidal metabolite discovered *in Streptomyces kasugaensis* [49], inhibits protein biosynthesis in microorganisms but not in mammals, since its toxicological features are excellent. Inhibition of plant pathogenic *Rhizoctonia solani* under in vitro conditions was assessed with the culture supernatant of *Streptomyces* sp., which showed that the tested Actinobacteria had the ability to reduce damping-off severity in tomato plants (**Table 6**).

The majority of microorganisms were identified as antagonists of plant-parasitic nematodes, in particular Actinobacteria, which are effectively used in biological control because of their ability to produce antibiotics. The *Streptomyces* species-producing avermectins show that high nematicidal compounds can be produced by soil-borne organisms. *Streptomyces avermitilis* produces ivermectin, having an efficient activity against *Wucheria bancroftii* [50]. Similarly,

PGPR can directly or indirectly affect the growth of plants in two common ways. Indirect growth happens when PGPR decreases or prevents the harmful effects of one or more damaging

various other antiparasitic compounds are produced from various *Streptomyces* sp.

#### **2.8. Pigments**

Microbe-oriented pigments are of great concern. Especially, Actinobacteria are characterized by the production of various pigments on natural or synthetic media and are considered an important cultural characteristic in describing the organisms. Generally, the morphological features of colonies and production of different pigments and aerial branching filaments are known as hyphae, giving them a fuzzy appearance. These pigments are usually various shades of blue, violet, red, rose, yellow, green, brown, and black, which can be dissolved in the medium or may be retained in the mycelium. These microbes also have the ability to synthesize and excrete dark pigments, melanin or melanoid, which are considered useful criteria for taxonomical studies in the textile industry (**Table 4**).

#### **2.9. Nanoparticle synthesis**

The chemical techniques of nanoparticle preparation are less expensive when produced in high quantities; however, the nanoparticles may be contaminated by precursor chemicals, toxic solvents, and risky by-products. As a result, the development of high-yield, low-charge, nontoxic effects, and beneficial environmental procedures for metallic nanoparticle synthesis, and thus the biological method of nanoparticle synthesis, is considered important. Actinobacteria are actually effective nanoparticle producers, showing a number of biological properties, including antibacterial, antifungal, anticancer, antibiofouling, antimalarial, antiparasitic, and antioxidant activities. *Streptomyces* and *Arthrobacter* genera have proved to be "nanofactories" for developing clean and nontoxic procedures for the preparation of silver and gold nanoparticles (**Table 5**).


**Table 4.** Exemples of pigments produced by some streptomyces species and their classification.


**Table 5.** Exemples of nanoparticules produced by some streptomyces species.

#### **2.10. Bioremediation**

*Streptomyces* have an important role in the recycling of organic carbon and are able to degrade complex polymers [43]. As reported, the wide use of petroleum hydrocarbons as chemical compounds and fuel in everyday life was considered well-known pollutants of large soil surfaces, causing serious environmental damage. Some studies proved the possible beneficial role of *Streptomyces* flora in the degradation of hydrocarbons [44, 45]. Many Actinobacterial strains are able to solubilize lignin and break down lignin-related compounds following the production of cellulose and hemicellulose-degrading enzymes and extracellular peroxidase [46]. Actinobacteria species are able to grow and live in oil-rich environments, and thus they could be in bioremediation to reduce oil contaminants.

#### **2.11. Control of plant diseases**

Results of new approaches to control plant diseases. Actinobacteria are potentially used in the agro-industry as a source of agroactive compounds of plant growth (rhizobacteria (polyglycerol polyricinoleate, PGPR) promoting) and for biocontrol [47, 48]. Approximately 60% of the new insecticides and herbicides derived from *Streptomyces* were discovered in the last 5 years*.* Kasugamycin, a bactericidal and fungicidal metabolite discovered *in Streptomyces kasugaensis* [49], inhibits protein biosynthesis in microorganisms but not in mammals, since its toxicological features are excellent. Inhibition of plant pathogenic *Rhizoctonia solani* under in vitro conditions was assessed with the culture supernatant of *Streptomyces* sp., which showed that the tested Actinobacteria had the ability to reduce damping-off severity in tomato plants (**Table 6**).

#### **2.12. Nematode control**

**Pigments** *Streptomyces* **strain Class** III Undecylprodigiosin *S. longispororuber* DSM 40599 Prodigiosin

Actinomycin *Streptomyces* sp. Phenoxazinone Granaticin *S. litmocidin* DSM 40164 Naphthoquinone Rhodomycin *Synodontis violaceus* DSM 40704 Anthracycline glycoside

Vitamin B12 or cobalamine can be synthesized through the fermentation of Actinobacteria [41, 42], and has aroused considerable interest in the possible production of vitamins through microbial fermentation. In addition, cobalt salts in media act as a general Actinobacteria precursor in producing vitamins. Because cobalt is a rather effective bactericidal agent, this precursor must be added carefully. The fermentations producing the antibiotics streptomycin, aureomycin, grisein, and neomycin produce vitamin B12 as well if the medium is supplemented with cobalt

Microbe-oriented pigments are of great concern. Especially, Actinobacteria are characterized by the production of various pigments on natural or synthetic media and are considered an important cultural characteristic in describing the organisms. Generally, the morphological features of colonies and production of different pigments and aerial branching filaments are known as hyphae, giving them a fuzzy appearance. These pigments are usually various shades of blue, violet, red, rose, yellow, green, brown, and black, which can be dissolved in the medium or may be retained in the mycelium. These microbes also have the ability to synthesize and excrete dark pigments, melanin or melanoid, which are considered useful criteria for taxonomical studies in

The chemical techniques of nanoparticle preparation are less expensive when produced in high quantities; however, the nanoparticles may be contaminated by precursor chemicals, toxic solvents, and risky by-products. As a result, the development of high-yield, low-charge, nontoxic effects, and beneficial environmental procedures for metallic nanoparticle synthesis, and thus the biological method of nanoparticle synthesis, is considered important. Actinobacteria are actually effective nanoparticle producers, showing a number of biological properties, including antibacterial, antifungal, anticancer, antibiofouling, antimalarial, antiparasitic, and antioxidant activities. *Streptomyces* and *Arthrobacter* genera have proved to be "nanofactories" for developing clean and nontoxic procedures for the preparation of silver

**Table 4.** Exemples of pigments produced by some streptomyces species and their classification.

IV Metacycloprodigiosin

**2.7. Vitamins**

108 Basic Biology and Applications of Actinobacteria

**2.8. Pigments**

the textile industry (**Table 4**).

**2.9. Nanoparticle synthesis**

and gold nanoparticles (**Table 5**).

without affecting the yields of antibiotic substances.

The majority of microorganisms were identified as antagonists of plant-parasitic nematodes, in particular Actinobacteria, which are effectively used in biological control because of their ability to produce antibiotics. The *Streptomyces* species-producing avermectins show that high nematicidal compounds can be produced by soil-borne organisms. *Streptomyces avermitilis* produces ivermectin, having an efficient activity against *Wucheria bancroftii* [50]. Similarly, various other antiparasitic compounds are produced from various *Streptomyces* sp.

#### **2.13. Enhancement of plant growth**

PGPR can directly or indirectly affect the growth of plants in two common ways. Indirect growth happens when PGPR decreases or prevents the harmful effects of one or more damaging


since earlier works have studied the IAA synthesis process in *Streptomyces* spp. This was the first investigation confirming IAA production according to new analytical methods, i.e. highperformance liquid chromatography and gas chromatography–mass spectrometry. Furthermore, Manulis et al. [53] described well the biosynthetic pathways of IAA in *Streptomyces.* On the other hand, Aldesuquy et al. [54] studied the effect of streptomycetes culture filtrates on wheat growth, showing a subesquent significant increase in shoot fresh mass, dry mass, length, and diameter statistically exhibited with some bacterial strains at different sample times. *Streptomyces olivaceoviridis* revealed a remarkable effect on yield components (spikelet number, spike length, and fresh and dry mass of the developing grain) of wheat plants. This activity may result from the increase in phytohormone bioavailability defined as PGPR produced, since all PGPR strains (*Streptomyces rimosus, Streptomyces rochei*, and *S. olivaceoviridis*) produce significant amounts of auxins (IAA),

Musty 1,2,7,7-Tetramethyl-2-norbornanol Potato-like 2-Isobutyl-3-methoxypyrazine or

2-isopropyl-3-methoxypyrazine

*Streptomyces* Secondary Metabolites http://dx.doi.org/10.5772/intechopen.79890 111

*Streptomyc***es strain Odor type Secondary metabolite**

**Table 7.** Odor-producing compounds from Actinobacteria.

*Streptomyces* sp. Earthy Trans-1,10-dimethyl-trans-9-decalol (geosmin)

Dhanasekaran et al. [55] obtained that the isolates *Streptomyces* sp., *Streptosporangium* sp., and *Micropolyspora* sp. presented with great larvicidal activity against *Anopheles* mosquito larvae. Rajesh et al. [56] prepared silver nanoparticles from *Streptomyces* sp. GRD cell filtrate and found remarkable larvicidal activity against *Aedes* and *Culex* vectors, causing transmission of dengue and filariasis. In addition, studies carried out on the larvicidal effect of Actinobacterial extracts against *Culex* larvae have shown that a concentration of 1000 ppm of the isolate *Streptomyces* sp. appeared as KA13-3 with 100% mortality and KA25-A with 90% mortality. Other secondary metabolites obtained from Actinobacteria (tetranectin [56], avermectins [57],

The work carried out by Gaines and Collins [60] on the metabolites of *Streptomyces odorifer* led them to conclude that the earthy odor is likely due to a combination of trivial compounds (acetic acid, acetaldehyde, ethyl alcohol, isobutyl alcohol, isobutyl acetate, and ammonia). Consequently, other components contributing to the odor could also be produced. Several odor-producing compounds have been defined from Actinobacteria (**Table 7**). Earthy odors in sufficiently treated water supplies led to considerable interest from consumers, who may classify water with these odors as harmful for human drinking needs. These odors are the second most common cause of odor problems recorded by water utilities, behind chlorine.

macrotetrolides [58], and flavonoids [59]) are classified as toxic to mosquitoes.

gibberellins, and cytokinins.

**2.16. Odor and flavor compound production**

**2.15. Biolarvicides**

**Table 6.** Antibiotics produced by the Actinobacteria that suppress various plant diseases.

microorganisms. This is mainly researched through biocontrol or the antagonism of soil plant pathogens. Particularly, the effects of pathogen invasion and establishment can be strongly prevented by colonization or the biosynthesis of antibiotics and other secondary metabolites. Direct growth promotes plant growth by PGPR when the plant is supplied with a bacterial synthesized compound, or when PGPR otherwise facilitates plant uptake of soil nutrients. Merriman [51] reported the use of *S. griseus* for seed treatment of barley, oat, wheat, and carrot to increase their growth. The isolate was originally selected for the biological control of *Rhizoctonia solani*. It has been reported that *Streptomyces pulcher*, *Streptomyces canescens*, and *Streptomyces citreofluores* were used in the control of bacterial, *Fusarium*, and *Verticillium* wilts, early blight, and bacterial canker of tomato.

Like most rhizobacteria, it seems highly probable that streptomycetes are capable of directly enhancing plant growth.

#### **2.14. Phytohormone production**

Manulis et al. [52] described plant hormone production, including indole-3-acetic acid (IAA), as well as the underlying pathways of synthesis by a variety of *Streptomyces* spp. (*Streptomyces violaceus, Streptomyces scabies*, *S. griseus*, *Streptomyces exfoliatus*, *Streptomyces coelicolor*, and *S. lividans*),


**Table 7.** Odor-producing compounds from Actinobacteria.

since earlier works have studied the IAA synthesis process in *Streptomyces* spp. This was the first investigation confirming IAA production according to new analytical methods, i.e. highperformance liquid chromatography and gas chromatography–mass spectrometry. Furthermore, Manulis et al. [53] described well the biosynthetic pathways of IAA in *Streptomyces.* On the other hand, Aldesuquy et al. [54] studied the effect of streptomycetes culture filtrates on wheat growth, showing a subesquent significant increase in shoot fresh mass, dry mass, length, and diameter statistically exhibited with some bacterial strains at different sample times. *Streptomyces olivaceoviridis* revealed a remarkable effect on yield components (spikelet number, spike length, and fresh and dry mass of the developing grain) of wheat plants. This activity may result from the increase in phytohormone bioavailability defined as PGPR produced, since all PGPR strains (*Streptomyces rimosus, Streptomyces rochei*, and *S. olivaceoviridis*) produce significant amounts of auxins (IAA), gibberellins, and cytokinins.

#### **2.15. Biolarvicides**

microorganisms. This is mainly researched through biocontrol or the antagonism of soil plant pathogens. Particularly, the effects of pathogen invasion and establishment can be strongly prevented by colonization or the biosynthesis of antibiotics and other secondary metabolites. Direct growth promotes plant growth by PGPR when the plant is supplied with a bacterial synthesized compound, or when PGPR otherwise facilitates plant uptake of soil nutrients. Merriman [51] reported the use of *S. griseus* for seed treatment of barley, oat, wheat, and carrot to increase their growth. The isolate was originally selected for the biological control of *Rhizoctonia solani*. It has been reported that *Streptomyces pulcher*, *Streptomyces canescens*, and *Streptomyces citreofluores* were used in the control of bacterial, *Fusarium*, and *Verticillium* wilts, early blight, and bacterial canker of tomato. Like most rhizobacteria, it seems highly probable that streptomycetes are capable of directly

**Disease** *Streptomyces* **strains Antibiotic produced** Asparagus root diseases *S. griseus* Faeriefungin Blotch of wheat *S. malaysiensis* Malayamycin Broad range of plant diseases *S. griseochromogenes* Blasticidin S Brown rust of wheat *S. hygroscopicus* Gopalamycin Damping-off of cabbage *S. padanus* Fungichromin

Grass seedling disease *S. violaceusniger* YCED9 Nigericin and guanidylfungin A

Phytophthora blight of pepper *S. humidus* Phenylacetic acid

Phytophthora blight of pepper *S. violaceusniger* Tubercidin Potato scab *S. melanosporofaciens* Geldanamycin

Powdery mildew *Streptoverticillium rimofaciens* Mildiomycin

Powdery mildew of cucumber *Streptomyces* sp. KNF2047 Neopeptin A and B Rice blast disease *S. kasugaensis* Kasugamycin Rice sheath blight *S. cacaoi* var. *Asoensis* Polyoxin B and D Root rot of pea geldanus *S. hygroscopicus* Geldanamycin Sheath blight of rice *S. hygroscopicus* var. *Limoneus* No. T-7545 Validamycin

EF-76 and FP-54

**Table 6.** Antibiotics produced by the Actinobacteria that suppress various plant diseases.

Manulis et al. [52] described plant hormone production, including indole-3-acetic acid (IAA), as well as the underlying pathways of synthesis by a variety of *Streptomyces* spp. (*Streptomyces violaceus, Streptomyces scabies*, *S. griseus*, *Streptomyces exfoliatus*, *Streptomyces coelicolor*, and *S. lividans*),

enhancing plant growth.

**2.14. Phytohormone production**

110 Basic Biology and Applications of Actinobacteria

Dhanasekaran et al. [55] obtained that the isolates *Streptomyces* sp., *Streptosporangium* sp., and *Micropolyspora* sp. presented with great larvicidal activity against *Anopheles* mosquito larvae. Rajesh et al. [56] prepared silver nanoparticles from *Streptomyces* sp. GRD cell filtrate and found remarkable larvicidal activity against *Aedes* and *Culex* vectors, causing transmission of dengue and filariasis. In addition, studies carried out on the larvicidal effect of Actinobacterial extracts against *Culex* larvae have shown that a concentration of 1000 ppm of the isolate *Streptomyces* sp. appeared as KA13-3 with 100% mortality and KA25-A with 90% mortality. Other secondary metabolites obtained from Actinobacteria (tetranectin [56], avermectins [57], macrotetrolides [58], and flavonoids [59]) are classified as toxic to mosquitoes.

#### **2.16. Odor and flavor compound production**

The work carried out by Gaines and Collins [60] on the metabolites of *Streptomyces odorifer* led them to conclude that the earthy odor is likely due to a combination of trivial compounds (acetic acid, acetaldehyde, ethyl alcohol, isobutyl alcohol, isobutyl acetate, and ammonia). Consequently, other components contributing to the odor could also be produced. Several odor-producing compounds have been defined from Actinobacteria (**Table 7**). Earthy odors in sufficiently treated water supplies led to considerable interest from consumers, who may classify water with these odors as harmful for human drinking needs. These odors are the second most common cause of odor problems recorded by water utilities, behind chlorine.
