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eviews Ajikumar et al. Table 1. Continued literature isoprenoids produced approach production yield Kang et al. 2005 199 lycopene screening of shot-gun library to identify genes that 4,700 µg/gDW enhanced lycopene production and combinatorial expression of these genes Alper et al. 2006 197 lycopene characterization of knockout strains for lycopene production 196 221,600 µg/L by high cell density fermentations and optimization of growth conditions Yuan et al. 2006 192 lycopene overexpressing the chromosomal isoprenoid pathway 6,000 µg/g DCW genes, dxs, idi, ispDFand ispB using strong bacteriophage T5 promoter Yoon et al. 2006 203 lycopene overexpression of genes encoding the synthesis of 102,000 µg/L lycopene together with a heterologous ipiHP1 gene; expression of genes encoding mevalonate kinase, phosphomevalonate kinase and IPP isomerase from S. pneumonia; supplementation of mevalonate and adding of surfactant Newman et al. 2006 180 amorpha-4,11-diene optimization of two-phase partitioning bioreactor for fermentation of amropha-4,11-diene producing strain 188 500,000 µg/L Yoon et al. 2007 204 lycopene expression of genes from the organisms P. agglomerans 60,000 µg/L and P. ananatis which both encodes the production of lycopene, combined with the expression of genes encoding mevalonate kinase, phosphomevalonate kinase and IPP isomerase from S. pneumonia; supplementation of mevalonate Pitera et al. 2007 205 mevalonate pathway optimization for balancing enzyme activity of the heterologous expressed amorpha-4,11-diene mevalonate pathway Jin and Stephanopoulos 2007 198 lycopene combination of overexpression targets identified by 16,000 µg/gDW screening of genomic libraries with knockout targets predicted by stoichiometric modeling Chang et al. 2007 181 8-hydroxycadinene and artemisinic acid expression of plant cytochrome P450s followed by 105,000 µg/L and 105,000 µg/L optimization 182 MOLECULAR PHARMACEUTICS VOL. 5, NO. 2
Terpenoids: Biosynthesis of Natural Product Drugs reviews Table 2. Summary of Terpenoids Produced in Yeast and Different Approaches for Improving the Production Yield literature isoprenoid produced organism approach amount produced Yamano et al. 1994 207 lycopene and -carotene S. cerevisiae expression of heterologous carotenoid genes on plasmids under 113 µg/gDW and 103 µg/gDW the control of native promoters derived from the yeast genome Miura et al. 1998 208 lycopene C. utilis expression of heterologous carotenoid genes on plasmids under 758 µg/gDW the control of native promoters derived from the yeast genome Miura et al. 1998 209 lycopene, -carotene C. utilis expression of codon optimized heterologous carotenoid genes on 1,100 µg/gDW, 400 µg/gDW and and astaxanthin plasmids 400 µg/gDW Shimada et al. 1998 214 lycopene C. utilis expression of heterologous carotenoid genes on plasmid 7,800 µg/gDW combined with deletion of one ERG9 allele in diploid strain together with overexpression of truncated HMG gene Jackson et al. 2003 210 epi-cedrol S. cerevisiae expression of heterologous gene encoding epi-cedrol synthase 370 µg/L combined with overexpression of truncated HMG1 gene in upc2-1 mating type a DeJong et al. 2005 211 taxadiene and taxadien-5R-ol S. cerevisiae heterologous expression of five sequential paclitaxel pathway taxadiene 1 mg/L and (taxadien-5R-ol) genes achieved at ∼25 µg/L Lindahl et al. 2006 212 amorpha-4,11-diene S. cerevisiae expression of heterologous gene encoding amorpha-4,11-diene 600 µg/L and 100 µg/L synthase on high-copy plasmid and integration in the chromosome Ro et al. 2006 206 amorpha-4,11-diene and S. cerevisiae expression of heterologous genes combined with overexpression 153,000 µg/L and 115,000 µg/L artemisinic acid of tHMG gene, down regulating the ERG9 gene by substitution of ERG9 promoter for MET3 promoter, overexpression of upc2-1, integration of additional tHMGR, overexpression of ERG20 Shiba et al. 2007 215 amorpha-4,11-diene S. cerevisiae overexpressing native ALD6 and mutated Acs from Salmonella enterica in the strains from Ro et al. 2006 223 120,000 µg/L Asadollahi et al. 2007 213 valencene, cubebol S. cerevisaie downregulating the ERG9 gene by substitution of ERG9 promoter 3,000 µg/L, 1,600 µg/L and 11,500 µg/L and patchoulol for MET3 promoter and expression of heterologous genes (nonspecific synthases results in a mix of isoprenoids) VOL. 5, NO. 2 MOLECULAR PHARMACEUTICS 183
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