## 3 _Apergillus_ Is a Microbial Chassis for Natural Product Synthesis
### Sesterterpenoids
#### 3.1.3. A. orgaze  
as a Chassis for Synthesis of Other Natural Products Polyketides  
Polyketides represent a structurally diverse class of natural products, characterized by their intricately assembled carbon skeletons derived from simple acyl building blocks [118]. More than 10,000 polyketide compounds have been discovered so far, among which clinically important representatives--including lovastatin (anti-cholesterol), erythromycinomycin (antibiotic), azithromycin (antibiotic), and rapamycin (immunosuppressant)--serve as indispensable therapeutic agents in modern medicine [119; 120]. With the development of synthetic biology and the rise of green manufacturing, an increasing number of researchers are employing _A. orgaze_ as a chassis to modify and optimize the synthesis methods of polyketide compounds continuously. For example, [PERSON] et al. heterologously expressed the citrinin biosynthetic genes in _A. orgaze_, with the non-reducing polyketide synthase gene (_pksCT_, annotated as _citS_) as the core component. Through heterologous co-expression of _citS_ and downstream tailoring of enzyme genes (_citA-citE_) in _A. orgaze_, they achieved high-titer production of citrinin, validating its biosynthetic pathway and highlighting _A. orgaze_ as a robust host for fungal polyketide biosynthesis [121]. Moreover, [PERSON] et al. successfully overexpressed the monacolin K (MK) gene cluster from _Monascus pilosus_ in _A. orgaze_, resulting in the production of the corresponding metabolite, MK [58]. Furthermore, [PERSON] et al. reconstituted the biosynthetic gene cluster of phonoidride B in _A. orgaze_ by using a genome editing-based hot-spot knock-in method, thereby elucidating the late-stage biosynthesis of phonoidrides [122]. Additionally, [PERSON] et al. identified a polyketide synthase (PKS, _herA_) in the basidiomycete _Hericium erinacus_ through genome mining. They cloned the _herA_ gene and subsequently heterologously expressed it in _A. orgaze_, successfully achieving the production of orsellinic acid (OA) [123]. Similarly, [PERSON] et al. identified the _Phy_ biosynthetic gene cluster from _Aspergillus chevalieri BYST01_, which is responsible for the biosynthesis of physcion, a bioactive polyketide natural product derived from both plants and microorganisms. Through heterologous expression of key genes (_PhyF_, _PhyG_, and \begin{table}
\begin{tabular}{c c c c c} \hline
**Natural Products** & **Structure Type** & **Gene Source** & **Heterologous Hosts** & **References** \\ \hline astellifadiene & sesterterpenoid & _Entericella variecolor_ & _A. orgaze NSAR1_ & [116] \\ quiannulatene & sesterterpenoid & _Entericella variecolor_ & _A. orgaze NSAR1_ & [99] \\ quiannulatic acid & sesterterpenoid & _NBRC32302_ & _A. orgaze NSAR1_ & [117] \\ asperterpenoid A & sesterterpenoid & _Talaromyces wortmannii_ & _A. orgaze NSAR_ & [117] \\ asperterpenoid B & sesterterpenoid & _ATCC 26942_ & _A. orgaze NSAR_ & [104] \\  & & _Aspergillus calidoustus_ & _A. orgaze NSAR_ & [104] \\  & & _CBS121601_ & _A. orgaze NSAR1_ & [80] \\  & & _Fusarium graminaarum_ & _A. orgaze NSAR1_ & [106] \\  & & _J1-012_ & _A. orgaze NSAR1_ & [107] \\  & & _Aspergillus caluleatus ATCC_ & _A. orgaze NSAR1_ & [107] \\  & & _16872_ & _A. orgaze NSAR1_ & [110] \\  & & _Apergillus fungiatis Af293_ & _A. orgaze NSAR1_ & [110] \\  & & _Acernouni fusidoides_ & _A. orgaze NSAR1_ & [111] \\  & & _ATCC 14700_ & _A. orgaze_ NSAR1_ & [111] \\  & & _Acernouni chrysogenum_ & _A. orgaze NSAR1_ & [22] \\  & & _ATCC 11550_ & _A. orgaze NSAR1_ & [12] \\  & & _Polytolypa hystricis_ & _A. orgaze NSAR1_ & [112] \\  & & _UIAMH7299_ & _A. orgaze NSAR1_ & [113] \\  & & _Humicola fuscoatra NRRL_ & _A. orgaze NSAR1_ & [113] \\ \hline \end{tabular}
\end{table} 
Table 1: Cont. _PhyL_) in _A. oryzae_, they successfully reconstructed the biosynthetic pathway of physcion, thereby elucidating the molecular mechanisms underlying its production [124].