# Biosynthesis of Edible Terpenoids: Hosts and Applications
## 3 Application of Terpenoid Microbial Cell Factories in the Food Industry
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Functions** & **Chemicals** & **Host** & & **Strategy** & **Yield** & **Reference** \\ \hline \multirow{8}{*}{Stevoside} & \multirow{8}{*}{_S. cerevisiae_} & (1) & Expressing HHG1 and down-regulating ERG9 to strengthen the supply of precursor GGPP; & \multirow{8}{*}{1149 mg/L} & \multirow{8}{*}{[97]} \\  & & & (2) & Selecting active direptes synthases by using the stevibid yield as an indicator; & & \\  & & & (3) & Fusion-expressing two direptes synthases; & & \\  & & & (4) & Combining directed evolution and fusion expression of two & & \\  & & & & glycosyltransferases to synthesize isvoidside; & & \\  & & & (5) & Enhancing the supply of UDP-glucose by expressing key enzymes. & & \\ \hline \multirow{8}{*}{Rehudioside M} & \multirow{8}{*}{_S. cerevisiae_} & (1) & Knocking out endogenous glycoside hydrolase SCW2 to inhibit the hydrolysis of stevisoxide; & & \\  & & & (2) & Identifying an efficient glycosyltransferase, UGT91D2, and co-expressing it with UG76G1 to convert stevoiside to Reb M via Red E; & & \\  & & & (3) & Devengressing UCP1 to strengthen the supply of sugar donor & 12.5 g/L & [98] \\  & & & & UDP-glucose; & \\  & & & (4) & Introducing SIR2 to prolong the growth cycle; & & \\  & & & (5) & Whole-cell catalyzing the production of Reb M using stevioside as the substrate. & & \\ \hline \multirow{8}{*}{Medicinal health food} & \multirow{8}{*}{Germanacre} & \multirow{8}{*}{_Y. lipolytica_} & (1) & Identifying the most efficient gemarceme A synthase (DIGAS); & & \\  & & & (2) & Fuused expression of DGAS-ERG20; & & \\  & & & (3) & Strengthening the expression of the MVA pathway through strong promoters and multi-copy integration; & & \\  & & & & (4) & Restraining the downstream squaine synthesis pathway by truncating the native promoter of ERG9 (Praco); & & \\  & & & (5) & Increasing the acetyl-CoA supply by reducing the activity of ACC1 and promoting lipid degradation. & & \\ \hline \multirow{8}{*}{Valence} & \multirow{8}{*}{_S. cerevisiae_} & (1) & Identifying an efficient gemarceme A synthase (LTC2) and integrating the sequence into genome; & & \\  & & & (2) & Increasing the flux of MVA pathway by over-expressing the key enzymes; & & \\  & & & & Regulating the competition squaine synthetic pathway by substituting & & \\  & & & & an inducible promoter that is feedback inhibited by ergosterol; & & \\  & & & (4) & Adjusting the copy number of heterologous LTC2; & & \\  & & & (5) & Fed-batch fermentation; & & \\  & & & & (6) & Centrifuging the broth and then heating the dodecane layer at 250 \({}^{\circ}\)C to obtain product \(\beta\)-element. & & \\ \hline \multirow{8}{*}{Valence} & \multirow{8}{*}{_S. cerevisiae_} & (1) & Performing adaptive laboratory evolution and obtaining a platform & & \\  & & & strain BN-91A, which can grow using mannitol as sole carbon source; & & \\  & & & (2) & Introducing valence pathway into BN-91A; & & \\  & & & (3) & Decreasing the branch pathway by downregulating ERG9 (squaine synthase) and disrupting BTS1 (GCPP); & & \\  & & & (4) & Increasing the MVA pathway by over-expressing HHG1 and ERG12 & 5.6 g/L & [101] \\  & & & & (2) & Increasing copy number of valence synthase (CrVS); & \\  & & & & (6) & Facilitating mannitol association by over-expressing mannitol & \\  & & & & dehydrogenase (DSF) and mannitol transporter (HKT13); & & \\  & & & & (7) & Enhancing NADPH supply by integrating NADH kinase (POSS) gene; & & \\  & & & & (8) & High cell-density fermentation. & & \\ \hline \multirow{8}{*}{Patchoul} & \multirow{8}{*}{_E. coli_} & (1) & Identifying another valence synthase (\(\underline{\varepsilon}\)gVS) with higher catalytic efficiency than CrVS; & & & \\  & & & Semi-directed mutagenesis and obtaining an \(\underline{\varepsilon}\)gVS mutant with the highest catalytic efficiency; & & & \\  & & & & Optimizing the biosynthetic pathway by increasing the copy number of key enzymes and changing promoters; & & \\  & & & & (4) & Coupling cell growth and biochemical pathways by controlling URA3 & & \\  & & & & expression with the GAL promoter; & & \\  & & & & & (5) & High-cell-density fermentation and purifying valence; & \\  & & & & (6) & Chemically transforming telemedicine to noorkatkone. & & \\ \hline \multirow{8}{*}{Patchoul} & \multirow{8}{*}{_E. coli_} & (1) & Semi-rationally designing and obtaining a PTS mutant PTS2\({}^{\text{c}}\)4197/11854A & & & \\  & & & & with higher substrate-binding affinity; & & \\  & & & & (2) & Expressing FPTS-(PTL), P-PTS2 fusion protein; & 970.1 mg/L & [103] \\  & & & & (3) & Deleting the competitive acetate synthetic pathway, & & \\  & & & & (4) & Enhancing efflux transporters MacAB and MbA. & & \\ \hline \multirow{8}{*}{Patchoul} & \multirow{8}{*}{_E. coli_} & (1) & Modifying and obtaining a PTS mutant PTS2 mutk; & & & \\  & & & & (2) & Deleting the cyclic cAMP synthesis pathway to alleviate glucose & & \\  & & & & repression; & & \\  & & & (3) & Constructing a pyruvate biosensor and using it to regulate glycolysis pathway. & & \\ \hline \multirow{8}{*}{Patchoul} & \multirow{8}{*}{_S. cerevisiae_} & (1) & Expressing FPTS-PTS fusing protein and HHG1; & & & \\  & & & (2) & Modifying of pathway by deleting ROX1, Y1064W, and YPL062W; & & \\  & & & & (3) & Enhancing ergosterol pathway by over-expressing ERG1 and ERG24; & & \\  & & & & Regulating NADPH supply by over-expressing PO55; & & \\ \cline{1-1}  & & & & Decreasing intracellular ROS by over-expressing cytoplasmic catalase & 1632 mg/L & [105] \\ \cline{1-1}  & & & & (6) & Rational engineered PTS and obtained PTS175 as; which could reduce production of the concomitant products of patchoul; & & \\ \cline{1-1}  & & & & (7) & High-density fermentation with Mg\({}^{2}\) addition. & & \\ \hline \hline \end{tabular}
\end{table}