## 3 The OSMAC Approach Mediated by Co-Culture  
More than a decade ago \"One Strain Many Compounds\" (OSMAC) was employed as a successful strategy for isolation and identification of up to 20 different new secondary metabolites from the _Streptomyces_[40]. OSMAC approaches cover different strategies, such as changing medium composition and cultivation status, or co-cultivation with other strain(s). The alteration of the media component has a prominent impact on obtaining new NPs from _Streptomyces_ through the OSMAC approach. For example, the chemical investigation of the extract from the marine-derived strain _Streptomyces_ sp. C34 grown on ISP2 (yeast malt extract agar) medium resulted in the isolation of four new ansamycin-type polyketides. However, only three compounds could be extracted from the modified ISP2 medium, which contained glycerol, rather than glucose [41]. _Streptomyces_ sp. DSM 14386 produced five new compounds (**17-21**) in medium supplemented with 1.5% NaCl, while this strain produced two brominated congeners (**22,23**) in medium containing 1.5% NaBr [42]. Similarly, a novel antibacterial cyclodepsipeptide, named NC-1(**24**), was produced by a red soil-derived strain _Streptomyces_ sp. FXJ1.172 when cultured in GYM medium supplemented with ferric ion [43].  
Similarly, the changes in culture conditions have a prominent impact on tuning the production of novel compounds in the OSMAC approach. _Streptomyces_ sp. CHQ-64 produced six new antifungal polyene-polyols reedsmycins A-F and two new cytotoxic hybrid isoprenoid alkaloids indotertine A and drimentine F in liquid medium under shaking condition, while this strain produced a new hybrid isoprenoid alkaloid dimentine I under static condition [44]. The culture of _Streptomyces_ sp. HZP-2216E in solid medium as 2216E and GYM (glucose-yeast extract medium), and liquid medium as GMSS (Gause's medium with sea salt) resulted in the isolation of two new compounds as 23-O-butyrylbafilomycin D, and streptozotocinylpyrazinole A, and a unique indolizinium alkaloid streptopterusacin A [45; 46].  
Recently, the OSMAC approach based on the co-culture method is a very popular approach of elicitation of cryptic biosynthetic pathways. The co-cultivation results in alteration of the environmental setting by incorporating the multi-dimensional interspecies interaction. This method not only involves physical interaction between the species but also involves cross-talks between their metabolic pathways or signaling cascades, thus, results in unprecedented activation of the biosynthesis of novel NPs from _Streptomyces_. The co-culture of _S. coelicolor_ M145 with other actinomycete strains (_Amyclatopsis_ sp. AA4, _Streptomyces_ sp. EP14, _Streptomyces_ sp. SPB74, and _Streptomyces viridochromogenes_ DSM 40736) resulted in the production of at least 12 different versions of a molecule called desferrioxamine [47]. Co-cultivation of _Streptomyces leeuwenhoekii_ C34 and _Aspergillus fumigatus_ MR2012 in ISP2 medium resulted in the yield of a new luteoride derivative, and a new speurotin derivative, whereas none of these compounds could be detected in axenic culture. When _S. leeuwenhoekii_ C58 was co-cultivated with _A. fumigatus_ MR2012, a lasso peptide chaxapeptide was produced, which displayed significant inhibitory effect on human lung cancer cell line A549 [48; 49].