# Recent Advances in the Heterologous Biosynthesis of Natural Products from _Streptomyces_
## 3 Selecting a Suitable Host for Heterologous _Streptomyces_ Products
### Other Hosts  
Naturally, _Streptomyces_ exhibits a slow growth rate (about 0.16-0.25 h\({}^{-1}\)) [70], and their species are many times more difficult to genetically engineer. In most cases, the BGCs corresponding to potent compounds are silent/cryptic or the production titers are only produced in a detectable range. The BGCs derived from the native organism can be introduced into surrogate hosts to overcome the undesirable biological features of native producers. _Streptomyces_ compounds were expressed heterologously in other hosts, such as _E. coli_, _P. putida_, _S. cerevisiae_, _B. subtilis_, _C. glutamicum_, and _R. erythropolis_. _S. cerevisiae_ is a generally recognized as safe (GRAS) organism with DNA recombinant stability, easy genome engineering, well-known genomics and proteomics, and a cell factory for producing natural products. Engineered _S. cerevisiae_ was successfully used to produce a high level of natural products from other sources, for example, artemisinin acid up to 100 mg/L [71], tetrahydroccannabinolic acid up to 8.0 mg/L, cannabididic acid, and tetrahydroccannabisurinic acid up to 4.8 mg/L [72]. Engineered _S. cerevisiae_ also produced some natural products from _Streptomyces_ with high titers, such as gamma aminobutyric acid up to 62.6 g/L [73] and cannabigerolic acid up to 299.8 mg/L [74]. _B. subtilis_ exhibits a rapid growth rate of 0.5 h\({}^{-1}\)[75], which facilitates its use for heterologous expression. In previous work, _B. subtilis_ was successfully used for the heterologous expression of secondary metabolites from _Streptomyces_, such as 6-deoxyythronolide B from _Sacharopolyspora erythraea_[76] and enniatin from _Fusarium oxysporum_[77]. Therefore, _B. subtilis_ is a promising host for the heterologous expression of BGCs from _Streptomyces_. _E. coli_ also exhibits fast growth with a growth rate of 2-3 h\({}^{-1}\)[78] and it is an easy target for genetic manipulation. Its native biochemistry, physiology, and metabolomics are extensively understood [79]. Natural products, such as isoprenoids, non-ribosomal peptides, alkaloids, and polyketides, were successfully biosynthesized in _E. coli_[79]. However, the disadvantage of using _E. coli_ for the heterologous expression of natural productsfrom _Streptomyces_ is the lack of building blocks and phosphopantetheinyl moiety in _E. coli_. Many complex enzymes were expressed in insoluble form in _E. coli_. _E. coli_ lacks some specific building blocks, such as propionyl-CoA, methylmalonyl-CoA, and benzoyl-CoA, which can be supplied to the culture [80] or an engineered strain can be used that could provide the necessary precursors [81]. Many factors should be considered when doing a heterologous expression in _E. coli_, such as cofactors, the functional generation of the holoenzymes, the copy number of BGCs, promoters, native regulatory elements, and transcription factors [82; 83]. Therefore, for the heterologous expression of BGCs, the specific genes must be introduced or re-engineered to produce attractive products. On the other hand, the BGCs were re-engineered for expression in _E. coli_. For example, type II PKS systems from _Streptomyces_ contains an insoluble ketosynthe chain length factor in _E. coli_. [PERSON] and co-workers developed a plug-and-play production system to express type II PKSs for generating aromatic polyketides. An iterative monomodular type I was used for minimal PKS (mPKS) components expressing type II PKS clusters in _E. coli_ using mPKS. They successfully used _Photorhabus luminescence_s mPKS combined with tailored enzymes from other organisms to produce anthraquinones, dianthrones, and benzoisochromanequinones [84]. [PERSON] et al. also successfully used mPKS to generate TW95C and dehydrodrapelomycin in _E. coli_[85]. _C. glutamicum_ is a GRAS strain, generates amino acids at a large scale, and highly resists aromatic compounds. _C. glutamicum_ belongs to _Actinomycetes_ and is closely related to _Streptomyces_.