From: Yeast cell factories for fine chemical and API production
Host organism | Engineering steps | Substrate | Product/Outcome | Ref | |
---|---|---|---|---|---|
Saccharomyces cerevisiae | 1) Introduction of the Erwinia uredovora carotenoid biosynthesis genes [216]crtE, crtB, crtI and crtY (→ β-carotene) and crtE, crtB and crtI (→ lycopene), respectively, under the control of S. cerevisiae promoters and terminators [221] | galactose |
β-Carotene: 0.103 mg/g [CDW] |  | |
 | 2) Introduction of Erwinia herbicola carotenoid biosynthesis genes for lycopene, β-carotene and zeaxanthin production under the control of S. cerevisiae promoters and terminators [222] |  |
Lycopene: 0.113 mg/g [CDW] | Â | |
 |  |  |
Zeaxanthin: 0.01% of CDW ~0.2 – 0.05 mg/g [CDW] |  | |
Candida utilis | 1) Introduction of synthetic, codon-optimized Erwinia uredovora carotenoid biosynthesis genes (crtE, crtB, crtI and crtY) [216] and Agrobacterium aurantiacum carotenoid biosynthesis genes (crtZ and crtW) [217] under the control ot C. utilis promoters and terminators: | glucose |
Astaxanthin: 0.4 mg/g [CDW] | Â | [219] |
 | - Astaxanthin: crtE, crtB, crtI, crtY, crtZ and crtW |  |
β-Carotene: 0.4 mg/g [CDW] |  | [219] |
 | - β-Carotene: crtE, crtB, crtI and crtY |  |  |  |  |
 | - Lycopene: crtE, crtB and crtI |  |  |  |  |
 | 2) Improving Lycopene yields [218] by disruption of the C. utilis squalene synthase gene (ERG9) and overex-pression of the catalytic domain of the C. utilis 3-hydroxy methylglutaryl CoA reductase gene (HMG) |  |
Lycopene: 1.1 mg/g [CDW][219] 7.8 mg/g [CDW][218] | Â | |
Saccharomyces cerevisiae (fen1) | 1) Transfer of expression cassettes for mature bovine adrenodoxin (ADX), adrenodoxin reductase (ADR), and side chain cleavage cytochrome P450 (P450scc) | galactose |
| 60 mg/L | [241] |
 | 2) Transfer of Arabidopsis thaliana Δ7-sterol reductase |  |  |  |  |
 | 3) Disruption of Δ22-sterol desaturase (one step of endogenous ergosterol biosynthetic pathway) |  |  |  |  |
Saccharomyces cerevisiae (fen1) | 1) Transfer of expression cassettes for mature bovine adrenodoxin (ADX), adrenodoxin reductase (ADR), and side chain cleavage cytochrome P450 (P450scc) | galactose |
| No value given | [241] |
 | 2) Transfer of Arabidopsis thaliana Δ7-sterol reductase |  |  |  |  |
 | 3) Disruption of Δ22-sterol desaturase (one step of endogenous ergosterol biosynthetic pathway) |  |  |  |  |
 | 4) Introduction of type II human 3β-hydroxy-steroid dehydrogenase-isomerase (3β-HSD) |  |  |  |  |
Saccharomyces cerevisiae | 1) Rerouting the ergosterol biosynthesis pathway | glucose/ethanol |
| 11.5 mg/L | [228] |
 | 2) Introduction of the mammalian-specific part of the hydrocortisone biosynthetic pathway |  |  |  |  |
 | 3) Inactivation of side reactions to steroid biosynthesis dead ends |  |  |  |  |
 | 4) Adjusting expression levels for optimized steroid channeling to hydrocortisone |  |  |  |  |
Saccharomyces cerevisiae | 1) Introduction of the Artemisia annua epicedrol synthase gene | galactose |
| 0.37 mg/L | [229] |
 | 2) Overexpression of a truncated Hydroxy-methylglutaryl CoA reductase (trHmg1p) |  |  |  |  |
 | 3) Mutation of the Upc2p transcription factor → introduction of the upc2-1 allele with G888D [242] |  |  |  |  |
 | 4) Employing the S.c. haploid mating type a |  |  |  |  |
Saccharomyces cerevisiae | 1) Introduction of five Taxol biosynthetic genes from Taxus species: geranylgeranyl disphosphate synthase (GGPPS), taxadiene synthase (TS), taxadiene 5α-hydroxylase (THY5a), taxadienol 5α-O-acetyl trans-ferase (TAT), taxoid 10β-hydroxylase (THY10b) with necessary modifications for the expression in S. c. | simple sugar (glucose, galactose) and [2-14C] mevalonic acid for radio-HPLC analysis |
taxadien-5α-ol: 0.025 mg/L no taxadien-5α-acetoxy-10β-ol in vivo |  | [230] |
 | 2) Due to restricted THY5a expression, only a very small amount of the intermediate taxadien-5α-ol and no taxadien-5α-acetoxy-10β-ol was detected in vivo [230] |  |  |  |  |
Saccharomyces cerevisiae | 1) Engineering the farnesyl pyrophosphate (FPP) biosynthetic pathway | simple sugar |
| ~32 mg/L | [226] |
 | 2) Introduction of the Artemisia annua L amorphadiene synthase gene (FPP → amorphadiene) |  |  |  |  |
 | 3) Cloning the A. annua CYP71AV1/CPR (3-step oxidation: amorphadiene → artemisinic acid) |  |  |  |  |
Saccharomyces cerevisiae | 1) Follow-up study of [226]: | glucose |
~380 mg/L ~120 mg/L | Â | [227] |
 | 2) Engineering the pyruvate dehydrogenase bypass (pyruvate to acetyl-CoA) by overexpression of |  |  |  |  |
 | - Salmonella acetyl-CoA synthetase variant (L641P) |  |  |  |  |
 | - S. cerevisiae cytosolic acetaldehyde dehydrogenase (ALD6) |  |  |  |  |
 | - In strain S. cerevisiae EPY224 [226] |  |  |  |  |
 | 3) Results: increased levels of mevalonate and amorpha-4,11-diene (~120 mg/L); generally applicable for isoprenoid production |  |  |  |  |