Metabolic engineering strategies for de novo biosynthesis of sterols and steroids in yeast

Bioresources and Bioprocessing

Table 2 De novo synthesis of typical steroids in yeast

Products	Strain	Approach			Cultivation mode	Yield/titer/content	References
Products	Strain	Genes deleted	Genes introduced	Genes overexpressed	Cultivation mode	Yield/titer/content	References
Pregnenolone	S. cerevisiae	ERG5	ADR, ADX, P450scc, ∆7RED	–	High-density culture	60 mg/L	(Duport et al. 1998)
Pregnenolone	S. cerevisiae	ERG5	Δ7RED, matADR, matADX, CYP11A1	–	High-density culture	2.9 ± 0.5 mg L⁻¹A₆₀₀ units	(Duport et al. 2003)
Pregnenolone	Y. lipolytica	ERG5	CYP11A1, ADR, ADX, DHCR7	–	5 L bioreactor	78.0 mg/L	(Zhang et al. 2019)
Progesterone	S. cerevisiae	ERG5	ADR, ADX, P450scc, ∆7RED, 3β-HSD	–	High-density culture	60 mg/L	(Duport et al. 1998)
Hydrocortisone	S. cerevisiae	ATF2, GCY1, YPR1	∆7RED, ARH1, CYP11A1, NCP1, CYP21A1, matADR, matADX, CYP17A1, CYP11B1, 3β-HSD	ARH1, CYP21A1	High-density culture	11.5 mg/L	(Szczebara et al. 2003)
Diosgenin	S. cerevisiae	ERG6, ATF2	DrDHCR7, DrDHCR7, DzinCYP90G6, VvCPR, VcCYP94N1	ERG20, ERG9, ERG1	Flask fermentation	10 mg/L	(Cheng et al. 2021)
Diosgenin	S. cerevisiae	ERG5, ERG6	PpCYP90G4, PpCYP94D108 or TfCYP90B50, TfCYP82J17, CPR	–	–	–	(Christ et al. 2019)

matADR mature form ADR; matADX mature form ADR; 3β-HSD encoding 3β-hydroxy steroid dehydrogenase/isomerase; GCY1/YPR1 encoding aldo-keto reductases; ARH1 encoding ADR-related homolog; NCP1 encoding NADPH P450 reductase; CYP21A1 encoding 21-steroid hydroxylase; CYP17A1 encoding 17α-steroid hydroxylase; CYP11B1 encoding 11β-steroid hydroxylase; VvCPR CPR from Vitis vinifera