**3. Antibiotics**

The inadequate use of current antibiotics has led to antibiotic resistance, which is a global threat because of the adaptation rate of microorganisms [17]. Natural product discovery as a potential solution to antibiotic resistance has been important if we recall the discovery of penicillin and streptomycin. Nevertheless, actinobacteria isolated from soil have already been widely exploited, limiting the search of new antibiotics [18].

Due to the latter, the need to search new microorganisms associated with higher life forms or from unknown environments such as marine and extreme ecosystems [19, 20], as well as co-cultivation techniques between antagonists strains have been useful [21, 22], as the case of the co-cultivation of a *Micromonospora* sp. with a *Rhodococcus* strain to enhance the production of keyicin [23], as well as the co-cultivation of a marine *Pestalotia* sp. with an unidentified bacteria to obtain pestalone which resulted in high activity against *Staphylococcus aureus* and *Enterococcus faecium* [24].

Among the examples of marine microbial sources is a *Streptomyces* strain isolated from a marine sediment in India that produced ala-geninthiocin along with val-geninthiocin, geninthiocin and staurosporine; all compounds were found to be effective against *Staphylococcus aureus* and *Candida albicans* [25]. Another example is tetrahydroanthra-γ-pyrone from marine *Streptomyces* sp. (isolated from Binzhou shell island), which presented activity against *Bacillus subtilis*, *Staphylococcus aureus* and *Enterococcus faecalis* with a minimum inhibitory concentration (MIC) from 3 to 46 μg/mL [26].

The presence of metals has been explored to increase the production of antibiotics, such as the presence of nickel chloride in the cultivation of *Streptomyces pratensis* (isolated from the east coast of China), which enhanced the production of angucycline-type antibiotics, with moderate antimicrobial activity against *Pseudomonas aeruginosa*, *Klebsiella pneumonia*, *Escherichia coli* and *Staphylococcus aureus* with a MIC of 16 μg/mL [27]. Other minerals that have been tested to increase antimicrobial production on other *Streptomyces* strains are magnesium, calcium, manganese, cobalt, copper and iron salts, where copper sulfate and iron chloride resulted in the best induction of antimicrobial biosynthesis [28].

The *Micromonospora* is *a* genus of actinobacteria known to produce other antibiotics such as aminorifamycins and sporalactams with a good antimicrobial activity against *Mycobacterium tuberculosis* [29], as well as phocoenamicins with a potent activity against *Staphylococcus aureus* and *Mycobacterium tuberculosis* (MIC 32–64 μg/mL); the differences in their activity are attributed to different functional groups in the macrocyclic core [30].

*Microorganisms as Alternative Sources of New Natural Products DOI: http://dx.doi.org/10.5772/intechopen.92697*

Marine fungi have been considered as antibiotic sources such as *Penicillum* sp. (isolated from the coast of China), which produced four new compounds (neocitreoviridin, 10z-isocitreoviridinol, penicillstresseol and isopencillstressol) in the presence of cobalt. Penicillstresseol and isopencillstressol presented a MIC of 0.5 μg/mL against *Staphylococcus aureus*, followed by 10z-isocitroviridinol with a MIC value of 1–4 μg/mL, while neocitreoviridin exhibited a strong activity against *Pseudomonas aeruginosa* with a MIC around 4 μg/mL [31].

Marine *Engyodontium album* (isolated from a sponge) produced six new polyketides, where engyodontochone A and engyodontochone B were the ones that exhibited the best antimicrobial activity against *Staphylococcus aureus*, which was better than that of chloramphenicol [32].

Emerimicin IV extracted from *Emericellopsis minima* (isolated from a bay in Chile) exhibited a strong antimicrobial activity against *Enterococcus faecalis* and moderate to low activity against *Staphylococcus aureus* with a MIC value of 12.5 and 100 μg/mL respectively [33].

Extremophiles have also been useful in the discovery of new antibiotics due to the extreme growth conditions such as salinity (>1.0 M NaCl), pH (<5.0, >8.0), temperature (1–15°C and >45°C) and pressure (380 atm and >500–1200 atm); such conditions can be found on oceans, hypersaline lakes, hot springs and hydrothermal vents, among other places [34]. Actinobacteria are known to survive a range of the conditions previously reviewed such as the ones isolated from Kazakhstan where screening for antagonistic strains against *Escherichia coli* and *Aspergillus niger* [35].

Co-cultivation techniques have also been used for antibiotic synthesis such as *Penicillium fuscum* with *Penicillium camemberti/clavigerum*, whose co-culture allowed the extraction and purification of new macrolides named berkeleylactones. Berkeleylactone A was the one that exhibited the best activity against *Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, Candida albicans* and *Candida glabrata* [36].
