Table 1. Recombinant production of FSMs in S. cerevisiae.
| Compounds | Application; function | Heterologous enzymes implemented in yeast | Manipulation of yeast native genes | Titer | Source |
|---|---|---|---|---|---|
| Polyketides | |||||
| 6-MSA | Agrochemical; plant disease resistance | 6-MSAS from P. patulum, surfactin PPTase (Sfp) from B. subtilis | NA | 1.7 g/l | [24] |
| 6-MSA | Agrochemical; plant disease resistance | 6-MSAS from P. patulum and PPTase (npgA) from A. nidulans | NA | >200 mg/l | [27] |
| 6-MSA | Agrochemical; plant disease resistance | 6-MSAS from P. patulum and npgA | Overexpression of acetyl-CoA carboxylase (ACC1) | 554 ± 26 mg/l | [31] |
| (R)-monocillin II | Pharmaceutical; potential anticancer effect as an inhibitor of Hsp90 | IPKSs, Rdc5 and Rdc1 from Pochonia chlamydosporia, PPTase (npgA) from A. nidulans | Deletion of genes that encode for vacuolar aspartyl protease (PEP4) and proteinase B (PRB1) | 15 mg/l | [32] |
| Cladosporin | Pharmaceutical; antimicrobial and plant-growth inhibitory activities, antimalarial effect as a result of inhibition of Plasmodium falciparum lysyl‐tRNA synthetase | PKSs (Cla2 and Cla3) from Cladosporium cladosporioides, PPTase (npgA) from A. nidulans | Deletion of PEP4 and PRB1 | 10 mg/l | [33] |
| Rubrofusarin | Pharmaceutical and food additive; pigment with antibiotic effects on both bacteria and fungi | PKS12, dehydratase (aurZ), and O-methyltransferase (aurJ) from Fusarium graminearum, PPTase from Aspergillus fumigatus | NA | 1.1 mg/l | [34] |
| Bikaverin | Pharmaceutical; antibacterial and anticancer activities | Type I PKS (Bik1), FAD-dependent monooxygenase (Bik2), O-methyltransferase (Bik3) and PPTase from Fusarium fujikuroi, npgA from A. nidulans | NA | 202.75 mg/l | [35] |
| Simvastatin | Pharmaceutical | PKS (LovB), thioesterase (LovG), cytochrome P450 monooxygenase (LovA), cytochrome P450 reductase (CPR), and AT variant (LovD9) from Aspergillus terreus, enoyl reductase (MlcG) from Penicillium citrinum | Deletion of PEP4, PRB1, and gene for pyruvate carboxylase (PYC2) | 55 mg/l | [36] |
| Terpenoids | |||||
| α-cadinol | Pharmaceutical; potential anticancer effect (selective, potent cytotoxicity in breast adenocarcinoma cells) | Sesquiterpene synthase (GME3634) from Lignosus rhinocerotis | Deletion of PEP4 and PRB1 | Detectable | [37] |
| FCdiene | Pharmaceutical; precursor of anticancer drug fusicoccin A | FCdiene synthase from Alternaria brassicicola UAMH 7474 (AbFS) | Overexpression of genes that encode for hydroxy-methyl-glutaryl coenzyme A reductase isoenzyme 1 missing the N terminal domain (tHMGR1), variant of transcription factor UPC2 (UPC2-1) that regulate the ergosterol metabolism | 20–240 mg/l | [38–40] |
| Trichodemol | Pharmaceutical and agrochemical; potential anticancer agent and fungicide | Trichodiene synthase (FgTRI5) from Fusarium graminearum and cytochrome P450 monooxygenase from Trichoderma harzianum (TaTRI4 and TaTRI11) | Overexpression of tHMGR1 and UPC2-1 | 252 μg/l | [41] |
| ABA | Agrochemical; phytohormone | Cytochrome P450 monooxygenase (bcaba1 bcab2), sesquiterpene cyclase (bcaba3), short-chain dehydrogenase/reductase (bcaba4), cytochrome P450 reductase (bccpr1) from Botrytis cinerea | Deletion of genes that encoding for lipid phosphate phosphatase (LPP1) and DGPP phosphatase (DPP1), swapping ERG9 promoter to glucose-dependent HXT1 promoter, overexpression of ERG20 and tHMG1 | 11 mg/l | [42] |
| AA derivatives | |||||
| NRPs | |||||
| ACV | Pharmaceutical; antibiotic precursor | ACV synthetase (pcbAB) from P. chrysogenum, PPTase from A. nidulans, P. chrysogenum, or B. subtilis | NA | 1 μg–1 mg/g dry cell weight | [43] |
| Benzylpenicillin | Pharmaceutical; antibiotic | npgA from A. nidulans, pcbAB, isopenicillin N synthase (pcbC), phenylacetyl CoA ligase(pclA), and acyl-coenzyme A:isopenicillin N acyltransferase (penDE) from P. chrysogenum | NA | 3 µg/l | [44] |
| Beauvericins | Pharmaceutical and agrochemical; antibiotic, anticancer and insecticidal effects | Beauvericin synthetase (BbBEAS) and ketoisovalerate reductase (KIVR) from Beauveria bassiana; PPTase (npgA) from A. nidulans | Deletion of PEP4 and PRB1 | 105.8 ± 2.1 mg/l | [45] |
| Bassianolide | Agrochemical; insecticidal effect | Bassianolide synthetase (BbBSLS) from Beauveria bassiana, PPTase (npgA) from A. nidulans | Deletion of PEP4 and PRB1 | 21.7 ± 0.1 mg/l | [45] |
| Other proteinogenic AA derivatives | |||||
| Psilocybin | Pharmaceutical; treatment of various psychological and neurological afflictions | Tryptophan decarboxylase (CrTdc) from Catharanthus roseus, cytochrome P450 monooxygenase (PcPsiH), N-methyltransferase (PcPsiM), 4-hydroxytryptamine kinase (PcPsiK), CPR (PcCpr) from Psilocybe cubensis | Deletion of transcriptional regulator RIC1 gene, overexpression of genes encoding for pentafunctional AROM protein (ARO1), bifunctional chorismate synthase and flavin reductase (ARO2), 3-deoxy-d-arabinose- heptulosonate-7-phosphate (DAHP) synthase (ARO4K229L), and anthranilate synthase (TRP2S65R,S76L) | 627 ± 140 mg/l | [46] |
| ERG | Nutraceutical; antioxidant | ERG biosynthesis protein 1 (NcEgt1) from Neurospora crassa, ERG biosynthesis protein 2 (CpEgt2) from Claviceps purpurea | NA | 598 ± 18 mg/l | [47] |
| ERG | Nutraceutical; antioxidant | Gfegt1 and Gfegt2 from Grifola frondosa | NA | 20.61 mg/l | [48] |
NA, not applicable.