## 3 _Apergillus_ Is a Microbial Chassis for Natural Product Synthesis
### Sesterterpenoids  
Sesterterpenoids are a relatively small group among terpenoids and are predominantly synthesized through cyclization of the linear precursor geranylfarnesyl diphosphate (GFPP) [99]. Although sesterterpenoids are the rarest of all isoprenoids, they are widely distributed in higher plants, microorganisms, insects, and marine invertebrate organisms, especially sponges, and exhibit diverse biological properties including anti-cancer, anti-inflammatory, antiprotozoan, antitubercular, and antifeedant activities [100; 101]. During a screening of putative diterpene synthase genes, [PERSON]'s group identified the first sesterterpene synthase (AcOS) from _Aspergillus clavatus_, which simultaneously possesses the functions of class I sesterterpene synthase and prenyltransferase. They used the _A. oryzae_ heterologous expression system and obtained seisterterpene ophiobolin F [102]. On this basis, [PERSON] et al. discovered a new ophiobolin F synthase (AcIdOS) in _Aspergillus calidoustus_, which is a homologous gene of AcOS. They achieved the heterologous expression of AcIdOS in _A. oryzae_ and elucidated the absolute structure of ophiobolin F and its potential biosynthesis pathway [103]. Similarly, [PERSON] et al. identified and characterized the bifunctional sesterterpene synthase EvQS by the genome mining approach; they introduced it into _A. oryzae_ for heterologous expression and successfully obtained quiannulatene and quiannulatic acid [99]. Additionally, [PERSON] et al. achieved heterologous expression in _A. oryzae_ of a small biosynthetic gene cluster from _Aspergillus calidoustus_. This gene cluster, composed of two genes, _acIdAS_ for a chimeric sesterterpene synthase and _acIdA-P450_ for a cytochrome P450 monooxygenase, enabled the biosynthesis of asperterpenol A and asperterpenol B [104]. Moreover, [PERSON] et al. discovered a unique sesterterpenoid gene cluster (consisting of _pstA_ and _pstB_) and heterologously expressed both genes in _A. oryzae_, resulting in the production of two new sesterterpenoids, penisentenol and penisentone [105]. Notably, [PERSON]'s group designed a further optimized _A. oryzae_ chassis through an automated and high-throughput (auto-HTP) biofoundry workflow. Using this platform, they reconstituted 39 terpenoid BGCs into 208 _A. oryzae_ strains and successfully elucidated the biosynthetic pathway for the sesterterpenoid mangicol J [80]. Recently, [PERSON] et al. successfully achieved the heterologous production of bioactive fungal sesterterpenoids variecolin and variecolactone in _A. oryzae_ by co-expressing the cytochrome P450 monooxygenase VrcB along with the sesterterpene synthase gene _vrcA_. Subsequently, they employed a series of _vrcB_ homologues that were individually co-expressed with _vrcA_ in the _A. oryzae_ system, yielding three novel variecolin analogs [106]. Triterpenoids and Steroids  
Triterpenoids possess versatile biological activities and are extensively utilized in the pharmaceutical, food, cosmetic, and chemical industries [107]. As a structurally diverse class of terpenoids, triterpenoids are ubiquitously distributed across natural sources and serve as a significant resource for drug discovery from natural products due to their anti-inflammatory, antibacterial, antiviral, anti-oxidant, anti-cardiovascular, anti-tumor, and immunomododulatory properties [108; 109]. [PERSON] et al. designated the _hel_ gene cluster and individually introduced it into _A. oryzae_. Heterologous expression of this nine-gene cluster in _A. oryzae_ enables the isolation of the fungi-derived triterpenoid antibiotic helvolic acid (-20 mg L\({}^{-1}\)) and the elucidation of its complete biosynthetic pathway [110]. Based on this, [PERSON] et al. first identified the biosynthetic gene cluster of fusidic acid, which is the only fusidane-type antibiotic that has been clinically used.