# Recent Advances in the Heterologous Biosynthesis of Natural Products from _Streptomyces_
## 3 Selecting a Suitable Host for Heterologous _Streptomyces_ Products
### Other Hosts
Several investigators reported that engineered _Corynebacterium_ could biosynthesize target compounds, such as alcohols, aromatic compounds, and other secondary metabolites. _Corynebacterium_ possesses endogenous 4'-phosphopantetheinyl transferase (PPTase), PptAc\({}_{\text{G}}\), which can be utilized in heterologous expression of type I PKS, and NPRS from _Streptomyces_[86]. For example, roseoflavin from _Streptomyces__dawonensis_ was produced in _C. glutamicum_ via the heterologous expression of its BGCs [87]. _P. putida_ is also a GRAS strain with a rapid growth rate of 0.3-0.6 h\({}^{-1}\)[88]. It has a high GC content in its genome and a wide range of PPTases, similar to _Streptomyces_[89]. _P. putida_ is a useful host for natural products because many natural products have been produced in this strain using heterologous expression [90]. For instance, flaviolin, monornamolipid, zeaxanthin, and prodigiosin were produced via the heterologous expression of their BGCs from _Streptomyces griseus_, _Pseudomonas aeruginosa_, _Pantoea ananatis_, and _Serratia marcescens_ in _P. putida_, respectively [91; 90]. However, _P. putida_ requires introducing intracellular substrates and other features for the expression of target products, such as methylmalonyl-CoA [92] and coumaoyl-CoA [93]. _R. erythropolis_ is an aerobic, non-motile, and Gram-positive bacteria with a high GC content in its genome, similar to the _Streptomyces_ genome. [PERSON] et al. demonstrated that _Rhodococcus_ is a candidate for the expression of BGCs from _Streptomyces_[94]. For example, kasugamycin from _Streptomyces kasugaensis_ was produced in _R. erythropolis_[94]. The processing of heterologous in different hosts is shown in Figure 2.  
From previous experiments, _Streptomyces_ spp., _S. cerevisiae_, _B. subtilis_, _E. coli_, _C. glutamicum_, _P. putida_, and _R. erythropolis_ were shown to be hosts for the heterologous expression of BGCs from _Streptomyces_. Some natural products, which were produced by heterologous expression in _Streptomyces_ and other hosts, are listed in Table 1. The successful heterologous expression of BGCs depends on many elements, such as regulators, promoters, terminators, ribosome binding sites (RBSs), riboswitches, and transfer ribonucleic acids (tRNAs). However, to achieve this, the host should be engineered by deleting unwanted BGCs, inducing transcriptional terminators, using riboswitches, engineering tRNAs, and deleting or inserting regulators. Figure 2: Processing of heterologous biosynthetic gene clusters. RBS, ribosome binding site; CDS, coding sequence; TAR, transformation-associated recombination; LLHR, linear-plus-linear homologous recombination-mediated recombineering; PISR, phage \(\phi\)BT1 integrase-mediated site-specific recombination; ExoCET, exonuclease combined with RecET recombination; DiPAC, direct pathway cloning; SSRTA, site-specific recombination-based tandem assembly; SIRA, serine integrase recombinational assembly; CATCH, Cas9-assisted targeting of chromosome segments; PfAgo-based AREs, _Pyrooccus furiosus_ Argonaute-protein based artificial restriction enzymes; AGOS, artificial gene operon assembly system; PCR, polymerase chain reaction.