2016
DOI: 10.1038/nature19769
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Abstract: A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such as β-farnesene (CH), a plant sesquiterpene with versatile industrial applications, is straightforward. However, S. cerevisiae uses a chemically… Show more

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Cited by 495 publications
(429 citation statements)
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“…Optimization of ribosome binding site for NudB [38] E. coli Geraniol 2.0 g L À1 Fed-batch, 68 h Two-phase fermentation platform [43] S. cerevisiae Geraniol 293 mg L À1 Fed-batch, 48 h Overexpression of idi1 and tHMG1 [44] E. coli Limonene 650 mg L À1 Batch, 72 h Principal Component Analysis of proteomics data to optimize MVA pathway protein expression levels [46] E. coli Myrcene 58 mg L À1 Batch, 72 h Heterologous expression of myrcene synthase from Quecrus ilex [96] E. coli Cineol 653 mg L À1 Batch, 48 h Chromosomal mutation of ispA; heterologous expression of cineol synthase from Streptomyces clavuligerus [49] E. coli Linalool 505 mg L À1 Batch, 48 h Chromosomal mutation of ispA; heterologous expression of cineol synthase from Streptomyces clavuligerus [49] E. coli Pinene 140 mg L À1 Batch, 24 h Evolved pinene synthase from Pinus taeda to decrease substrate inhibition [48] E. coli Sabinene 2.7 g L À1 Fed-batch, 24 h Heterologous expression of gpps2 from Abies grandis and sabinene synthase from Salvia pomifera [52] S. cerevisiae Sabinene 18 mg L À1 Batch a) Altering a squalene synthase (erg20p) for GPP specificity [53] E. coli Farnesene 1.1 g L À1 Batch, 96 h In vitro measurement of MVA enzyme activity; balanced expression based on in vitro activity of heterologous pathway [55] S. cerevisiae Farnesene 130 g L À1 Fed-batch, 5-6 d a) Rewiring central carbon metabolism to enhance cytosolic CoA availability [56] E. coli Bisabolene 1.2 g L À1 Batch, 72 h Principal Component Analysis of proteomics data to optimize MVA pathway protein expression levels [46] E. coli b-Caryophyllene 1.5 g L À1 Fed-batch, 72 h Balanced overexpression of MVA and DXP pathway enzymes [58] Fatty acids E. coli Fatty acids 5.2 g L À1 Batch, 72 h Dynamic regulation and control; tuning expression of FadR [62,66] E. coli Fatty acids 8.6 g L À1 Fed-batch, 70 h Optimization of transcription levels in three arbitrary modules within fatty-acid biosynthesis [67] E. coli Fatty acids 3.9 g L À1 Fed-batch, 44 h Dynamic control using transcriptional regulator FapR [61] E. coli Fatty acids 7 g L À1 Batch, 24 h Reversed b-oxidation cycle; overexpression of FadBA and select thioesterases in strain RB03 (RB02 DyqhD DfucO DfadD) [64] E. coli Branched fatty acids 276 mg L À1 Batch, 48 h Incomplete lipoylation of 2-oxoacid dehydrogenases [76] E. coli Fatty acids 694 mg L À1 Batch, 48 h Heterologous expression of Val, Leu, Ile biosynthetic pathways; overexpression of bFabH2 and 'TesA [74] E. coli Fatty acids 21.5 g L À1 Fed-batch, 43 h Ensemble-based selection of bacterial strains u...…”
Section: G L à1mentioning
confidence: 99%
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“…Optimization of ribosome binding site for NudB [38] E. coli Geraniol 2.0 g L À1 Fed-batch, 68 h Two-phase fermentation platform [43] S. cerevisiae Geraniol 293 mg L À1 Fed-batch, 48 h Overexpression of idi1 and tHMG1 [44] E. coli Limonene 650 mg L À1 Batch, 72 h Principal Component Analysis of proteomics data to optimize MVA pathway protein expression levels [46] E. coli Myrcene 58 mg L À1 Batch, 72 h Heterologous expression of myrcene synthase from Quecrus ilex [96] E. coli Cineol 653 mg L À1 Batch, 48 h Chromosomal mutation of ispA; heterologous expression of cineol synthase from Streptomyces clavuligerus [49] E. coli Linalool 505 mg L À1 Batch, 48 h Chromosomal mutation of ispA; heterologous expression of cineol synthase from Streptomyces clavuligerus [49] E. coli Pinene 140 mg L À1 Batch, 24 h Evolved pinene synthase from Pinus taeda to decrease substrate inhibition [48] E. coli Sabinene 2.7 g L À1 Fed-batch, 24 h Heterologous expression of gpps2 from Abies grandis and sabinene synthase from Salvia pomifera [52] S. cerevisiae Sabinene 18 mg L À1 Batch a) Altering a squalene synthase (erg20p) for GPP specificity [53] E. coli Farnesene 1.1 g L À1 Batch, 96 h In vitro measurement of MVA enzyme activity; balanced expression based on in vitro activity of heterologous pathway [55] S. cerevisiae Farnesene 130 g L À1 Fed-batch, 5-6 d a) Rewiring central carbon metabolism to enhance cytosolic CoA availability [56] E. coli Bisabolene 1.2 g L À1 Batch, 72 h Principal Component Analysis of proteomics data to optimize MVA pathway protein expression levels [46] E. coli b-Caryophyllene 1.5 g L À1 Fed-batch, 72 h Balanced overexpression of MVA and DXP pathway enzymes [58] Fatty acids E. coli Fatty acids 5.2 g L À1 Batch, 72 h Dynamic regulation and control; tuning expression of FadR [62,66] E. coli Fatty acids 8.6 g L À1 Fed-batch, 70 h Optimization of transcription levels in three arbitrary modules within fatty-acid biosynthesis [67] E. coli Fatty acids 3.9 g L À1 Fed-batch, 44 h Dynamic control using transcriptional regulator FapR [61] E. coli Fatty acids 7 g L À1 Batch, 24 h Reversed b-oxidation cycle; overexpression of FadBA and select thioesterases in strain RB03 (RB02 DyqhD DfucO DfadD) [64] E. coli Branched fatty acids 276 mg L À1 Batch, 48 h Incomplete lipoylation of 2-oxoacid dehydrogenases [76] E. coli Fatty acids 694 mg L À1 Batch, 48 h Heterologous expression of Val, Leu, Ile biosynthetic pathways; overexpression of bFabH2 and 'TesA [74] E. coli Fatty acids 21.5 g L À1 Fed-batch, 43 h Ensemble-based selection of bacterial strains u...…”
Section: G L à1mentioning
confidence: 99%
“…Most noteworthy, Amyris recently engineered S. cerevisiae strains for production of farnesene at www.advancedsciencenews.com www.biotechnology-journal.com www.advancedsciencenews.com www.biotechnology-journal.com titers of 130 g L À1 in fed-batch fermentation by introducing novel pathways to increase cytosolic acetyl-CoA levels. [56] A monocyclic sesquiterpene bisabolene has also been discovered as a precursor for diesel fuel replacement, and its microbial production was demonstrated in both E. coli and in S. cerevisiae at a comparable level to farnesene. [57] In E. coli, further engineering aided by proteomics improved titers to 1.2 g L À1 by balancing pathway enzyme levels in vivo.…”
Section: Sesquiterpenesmentioning
confidence: 99%
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“…In one study by Meadows et al [60], a S. cerevisiae strain was developed by completely overhauling the native metabolic network involved in acetyl-CoA supply by incorporating several synthetic pathways which directly resulted in increased recombinant terpenoid levels.…”
Section: Terpenoidsmentioning
confidence: 99%
“…Recent developments in synthetic biology enable introduction of entire metabolic pathways and, thereby, new functionalities for product formation and substrate consumption, into microbial cells (1). However, industrial relevance of the resulting strains critically depends on optimal interaction of the newly introduced pathways with the core metabolism of the host cell.…”
mentioning
confidence: 99%