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2018 | OriginalPaper | Chapter

3. Advances and Tools in Engineering Yeast for Pharmaceutical Production

Authors : Aravind Madhavan, Raveendran Sindhu, K. B. Arun, Ashok Pandey, Parameswaran Binod

Published in: Biosynthetic Technology and Environmental Challenges

Publisher: Springer Singapore

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Abstract

Production of recombinant pharmaceutical protein is a multibillion-dollar industry and plays a crucial role in treatment of many diseases. Among the several potent microbial production systems, yeast offers several advantages in production of pharmaceutically important proteins due to its unicellular nature, easy gene manipulation, cost-effectiveness and fast growth and incorporates post-translational modifications in heterologous proteins. Saccharomyces cerevisiae is the widely used heterologous host for the production of medically important proteins and drugs; however, several non-conventional yeast species including Hansenula polymorpha, Pichia pastoris, and Yarrowia lipolytica are also gaining much attention as alternative heterologous hosts for the industrial production of therapeutic proteins. In this chapter, most recent advances in glycoengineering of yeast for successful therapeutic pharmaceutical production, current progress in humanization of yeast and various interventions in the secretory mechanisms and pathways in yeast for the improvement of the production of pharmaceutical proteins are overviewed. In addition, emerging genetic, omics, systems and synthetic biology tools and other technologies to enhance the efficiency of yeast pharmaceutical proteins are precisely discussed. The use of synthetic biology tools in yeast for the production of pharmaceuticals is clearly entering a new phase right now. Combination of yeast systems biology data with synthetic biology will open new vistas to better production, improved glycosylation and secretory mechanism. The application of currently available synthetic biology tools like CRISPR/Cas9 in yeast pathway engineering is also discussed.

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Ahmad M, Hirz M, Pichler H, Schwab H (2014) Protein expression in Pichia pastoris: recent achievements and perspectives for heterologous protein production. Appl Environ Microbiol 98:5301–5317

Amano K, Chiba Y, Kasahara Y, Kato Y, Kaneko MK, Kuno A, Ito H, Kobayashi K, Hirabayashi J, Jigami Y, Narimatsu H (2008) Engineering of mucin-type human glycoproteins in yeast cells. Proc Nat Acad Sci USA 105(9):3232–3237CrossRef

Anelli T, Sitia R (2008) Protein quality control in the early secretory pathway. EMBO J 27:315–327CrossRef

Baeshen NA, Baeshe MN, Sheikh A, Bora RS, Ahmed M, Ramadan HI, Saini K, Redwan EM (2014) Cell factories for insulin production. Microb Cell Fact 13:141CrossRef

Bao Z, Xiao H, Liang J, Zhang L, Xiong X, Sun N (2015) Homologyintegrated CRISPR-Cas (HI-CRISPR) system for one-step multigene disruption in Saccharomyces cerevisiae. ACS Synth Biol 4:585–594CrossRef

Bause E (1983) Structural requirements of N-glycosylation of proteins. Stud Proline Peptides Conformational Probes Biochem J 209:331–336

Becker SA, Feist AM, Mo ML, Hannum G, Palsson B, Herrgard MJ (2007) Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox. Nat Protoc 2:727–738CrossRef

Bretthauer RK (2003) Genetic engineering of Pichia pastoris to humanize N-glycosylation of proteins. Trends Biotechnol 21:459–462CrossRef

Brophy JAN, Voigt CA (2014) Principles of genetic circuit design. Nat Methods 11:508–520CrossRef

Burda P, Aebi M (1998) The ALG10 locus of Saccharomyces cerevisiae encodes the alpha-1,2 glucosyltransferase of the endoplasmic reticulum: the terminal glucose of the lipid linked oligosaccharide is required for efficient N-linked glycosylation. Glycobiology 8:455–462CrossRef

Camirand A, Heysen A, Grondin B, Herscovics A (1991) Glycoprotein biosynthesis in Saccharomyces cerevisiae. Isolation and characterization of the gene encoding a specific processing alpha-mannosidase. J Biol Chem 266:15120–15127

Carrera J, Jaramillo A (2013) Automated design of bacterial genome sequences. BMC Syst Biol 7:108

Caspeta L, Castillo T, Nielsen J (2015) Modifying yeast tolerance to inhibitory conditions of ethanol production processes. Front Bioeng Biotechnol 3:184CrossRef

Chan LY, Kosuri S, Endy D (2005) Refactoring bacteriophage T7. Mol Syst Biol 1:0018

Cho EY, Cheon SA, Kim H, Choo J, Lee DJ, Ryu HM, Rhee SK, Chung BH, Kim JY, Kang HA (2010) Multiple-yapsin-deficient mutant strains for high-level production of intact recombinant proteins in Saccharomyces cerevisiae Biotechnol. 149(1–2):1–7

Chou C, Chang W, Chiu C, Huang C, Huang H (2009) FMM: a web server for metabolic pathway reconstruction and comparative analysis. Nucleic Acids Res 37:W129–W134CrossRef

Chubukov V, Gerosa L, Kochanowski K, Sauer U (2014) Coordination of microbial metabolism. Nat Rev Microbiol 12:327–340CrossRef

Chung BH, Park KS (1998) Simple approach to reducing proteolysis during the secretory production of human parathyroid hormone in Saccharomyces cerevisiae. Biotechnol Bioeng 57:245–249CrossRef

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N (2013) Multiplex genome engineering using CRISPR/Cas systems Science 339:819–823

Conibear E, Stevens TH (1998) Multiple sorting pathways between the late Golgi and the vacuole in yeast. Biochim Biophys Acta 1404:211–230CrossRef

Cvijovic M, Olivares-Hernández R, Agren R, Dahr N, Vongsangnak W, Nookaew I, Patil KR, Nielsen J (2010) BioMet toolbox: genome-wide analysis of metabolism. Nucleic Acids Res 38:W144–W149CrossRef

De Pourcq K, Vervecken W, Dewerte I, Valevska A, Van Hecke A, Callewaert N (2012a) Engineering the yeast Yarrowia lipolytica for the production of therapeutic proteins homogeneously glycosylated with Man₈GlcNAc₂ and Man₅GlcNAc₂. Microb Cell Fact 11:53CrossRef

De Pourcq K, Tiels P, Van Hecke A, Geysens S, Vervecken W, Callewaert N (2012b) Engineering Yarrowia lipolytica to produce glycoproteins homogeneously modified with the universal Man3GlcNAc2 N-glycan core. PLoS ONE 7(6):e39976CrossRef

De Pourcq K, Vervecken W, Dewerte I et al (2012c) Engineering the yeast Yarrowia lipolytica for the production of therapeutic proteins homogeneously glycosylated with Man8GlcNAc2 and Man5GlcNAc2. Microb Cell Fact 11:53CrossRef

De Schutter K, Lin YC, Tiels P, Van Hecke A, Glinka S, Weber- Lehmann J, Rouze P, Van de Peer Y, Callewaert N (2009) Genome sequence of the recombinant protein production host Pichia pastoris. Nat Biotechnol 27:561–566CrossRef

Dujon B, Sherman D, Fischer G et al (2004) Genome evolution in yeasts Nature 430:35–44

Durante Rodríguez G, Mancheño JM, Díaz E, Carmona M (2016) Refactoring the λ phage lytic/lysogenic decision with a synthetic regulator. Microbiol Open 5:575–581

Ecker M, Mrsa V, Hagen I, Deutzmann R, Strahl S, Tanner W (2003) O-mannosylation precedes and potentially controls the N-glycosylation of a yeast cell wall glycoprotein. EMBO Rep 4:628–632CrossRef

Eiden-Plach A, Zagorc T, Heintel T, Carius Y, Breinig F, Schmitt MJ (2004) Viral preprotoxin signal sequence allows efficient secretion of green fluorescent protein by Candida glabrata, Pichia pastoris, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. Appl Environ Microbiol 70:961–966CrossRef

Ellgaard L, Helenius A (2003) Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4:181–191CrossRef

Endy D, KnightJr TF (2008) Engineering BioBrick vectors from BioBrick parts. J Biol Eng 2:5CrossRef

Feng Y, De Franceschi G, Kahraman A, Soste M, Melnik A, Boersema PJ, de Laureto PP, Nikolaev Y, Oliveira AP, Picotti P (2014) Global analysis of protein structural changes in complex proteomes. Nat Biotechnol 32:1036–1044CrossRef

Fidan O, Zhan J (2015) Recent advances in engineering yeast for pharmaceutical protein production. RSC Adv 5:86665CrossRef

Finnis CJA, Payne T, Hay J et al (2010) High-level production of animal free recombinant transferrin from Saccharomyces cerevisiae. Microb Cell Fact 9:87CrossRef

Fuller RS, Brake AJ, Thorner J (1989) Intracellular targeting and structural conservation of a prohormone-processing endoprotease. Science 246:482–486CrossRef

Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA, Smith HO (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Meth 6:343–345CrossRef

Giga-Hama Y (1997) Fission yeast Schizosaccharomyces pombe: an attractive host for heterologous protein production. In: Giga- Hama Y, Kumagai H (eds) Foreign gene expression in fission yeast Schizosaccharomyces pombe. Springer, Berlin, pp 3–28CrossRef

Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE et al (2013) CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:442–451CrossRef

Goffeau A, Barrell BG, Bussey H et al (1996) Life with 6000 genes. Science 274:547–563CrossRef

Gonzalez-Lopez CI, Szabo R, Blanchin-Roland S, Gaillardin C (2002) Genetic control of extracellular protease synthesis in the yeast Yarrowia lipolytica. Genetics 160:417–427

Goodman M (2009) Market watch: sales of biologics to show robust growth through to 2013. Nat Rev Drug Discovery 8:837CrossRef

Guerfal M, Ryckaert S, Jacobs PP, Ameloot P, van Craenenbroeck K, Derycke R, Callewaert N (2010) The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins. Microb Cell Fact 9:49–60CrossRef

Hamilton SR, Gerngross TU (2007) Curr Opin Biotechnol 18:387–392CrossRef

Hamilton SR, Davidson RC, Sethuraman N, Nett JH, Jiang Y, Rios S, Bobrowicz P, Stadheim TA, Li H, Choi BK, Hopkins D, Wischnewski H, Roser J, Mitchell T, Strawbridge RR, Hoopes J, Wildt S, Gerngross TU (2006) Humanization of yeast to produce complex terminally sialylated glycoproteins. Science 313(5792):1441–1443

Hamilton SR, Cook WJ, Gomathinayagam S, Burnina I, Bukowski J, Hopkins D, Schwartz S, Du M, Sharkey NJ, Bobrowicz P, Wildt S, Li H, Stadheim TA, Nett JH (2013) Production of sialylated O-linked glycans in Pichia pastoris. Glycobiology 23(10):1192–1203CrossRef

Harmsen M, Bruyne M, Raué H, Maat J (1996) Overexpression of binding protein and disruption of the PMR1 gene synergistically stimulate secretion of bovine prochymosin but not plant thaumatin in yeast. Appl Microbiol Biotechnol 46:365–370CrossRef

Horwitz AA, Walter JM, Schubert MG, Kung SH, Hawkins K, Platt DM et al (2015) Efficient multiplexed integration of synergistic alleles and metabolic pathways in yeasts via CRISPR-Cas. Cell Systems 1:1–9CrossRef

Hou J, Tyo KE, Liu Z, Petranovic D, Nielsen J (2012) Metabolic engineering of recombinant protein secretion by Saccharomyces cerevisiae. FEMS Yeast Researh. 12:491–510CrossRef

Idiris A, Tohda H, Sasaki M, Okada K, Kumagai H, Giga-Hama Y, Takegawa K (2010a) Enhanced protein secretion from multiproteasedeficient fission yeast by modification of its vacuolar protein sorting pathway. Appl Microbiol Biotechnol 85:667–677CrossRef

Idiris A, Tohda H, Kumagai H, Takegawa K (2010b) Engineering of protein secretion in yeast: strategies and impact on protein production. Appl Microbiol Biotechnol 86:403–417CrossRef

Iwaki T, Hosomi A, Tokudomi S, Kusunoki Y, Fujita Y, Giga-Hama Y, Tanaka N, Takegawa K (2006) Vacuolar protein sorting receptor in Schizosaccharomyces pombe. Microbiology 152:1523–1532CrossRef

Jiang M, Stephanopoulos G, Pfeifer BA (2012) Downstream reactions and engineering in the microbially reconstituted pathway for Taxol. Appl Microbiol Biotechnol 94:841–849CrossRef

Jønson L, Rehfeld JF, Johnsen AH (2004) Enhanced peptide secretion by gene disruption of CYM1, a novel protease in Saccharomyces cerevisiae. Eur J Biochem 271:4788–4797CrossRef

Jung YK, Kim TY, Park SJ, Lee SY (2010) Metabolic engineering of Escherichia coli for the production of polylactic acid and its copolymers. Biotechnol Bioeng 105:161–171CrossRef

Kakule TB, Lin Z, Schmidt EW (2014) Combinatorialization of fungal polyketide synthase—peptide synthetase hybrid proteins. J Am Soc 136:17882–17890

Kalir S, McClure J, Pabbaraju K, Southward C, Ronen M, Leibler S, Surette MG, Alon U (2001) Ordering genes in a flagella pathway by analysis of expression kinetics from living bacteria. Science 292:2080–2083CrossRef

Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopaedia of genes and genomes. Nucleic Acids Res 28:27–30CrossRef

Kang HA, Choi ES, Hong WK, Kim JY, Ko SM, Sohn JH, Rhee SK (2000) Proteolytic stability of recombinant human serum albumin secreted in the yeast Saccharomyces cerevisiae. Appl Microbiol Biotechnol 53:575–582CrossRef

Kauffman K, Pridgen E, Fr D, Dhurjati P, Robinson A (2002) Decreased protein expression and intermittent recoveries in BiP levels result from cellular stress during heterologous protein expression in Saccharomyces cerevisiae. Biotechnol Prog 18:942–950CrossRef

Kida Y, Morimoto F, Sakaguchi M (2007) Two translocating hydrophilic segments of a nascent chain span the ER membrane during multispanning protein topogenesis. J Cell Biol 179:1441–1452CrossRef

Kida Y, Morimoto F, Sakaguchi M (2009) Signal anchor sequence provides motive force for polypeptide chain translocation through the endoplasmic reticulum membrane. J Biol Chem 284:2861–2866CrossRef

Kim H, Yoo SJ, Kang HA (2014) FEMS Yeast Res 15:1–16

Kim H, Yoo SJ, Kang HA (2015) Yeast synthetic biology for the production of recombinant therapeutic proteins. FEMS Yeast Res 15:1–16CrossRef

King ZA, Lloyd CJ, Feist AM, Palsson BO (2015) Next-generation genome-scale models for metabolic engineering. Curr Opin Biotechnol 35:23–29CrossRef

Komeda T, Sakai Y, Kato N, Kondo K (2002) Construction of protease-deficient Candida boidinii strains useful for recombinant protein production: cloning and disruption of proteinase A gene (PEP4) and proteinase B gene (PRBI). Biosci Biotechnol Biochem 66:628–663CrossRef

Kosuri S, Church GM (2014) Large-scale de novo DNA synthesis: technologies and applications. Nat Meth 11:499–507CrossRef

Lee JW, Kim TY, Jang Y, Choi S, Lee SY (2011) Systems metabolic engineering for chemicals and materials. Trends Biotechnol 29:370–378CrossRef

Lepenies B, Seeberger PH (2014) Simply better glycoproteins. Nat Biotechnol 32:443–445CrossRef

Liu L, Redden H, Alper HS (2013) Frontiers of yeast metabolic engineering: diversifying beyond ethanol and Saccharomyces. Curr Opin Biotechnol 24(6):1023–30

Madhavan A, Sukumaran RK (2016) Secreted expression of an active human interferon—beta (HuIFNβ) in Kluyveromyces lactis. Eng Life Sci 16:379–385CrossRef

Martinez JL, Liu L, Petranovic D, Nielsen J (2012) Pharmaceutical protein production by yeast: towards production of human blood proteins by microbial fermentation. Curr Opin Biotechnol 23:965–971CrossRef

Mattanovich D, Branduardi P, Dato L, Gasser B, Sauer M, Porro D (2012) Recombinant protein production in yeasts. Methods Mol Biol 824:329–358CrossRef

Mavromatis K, Chu K, Ivanova N, Hooper SD, Markowitz VM, Kyrpides NC (2009) Gene context analysis in the Integrated Microbial Genomes (IMG) data management system. PLoS ONE 4:e7979CrossRef

Medema MH et al (2011) Anti SMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 39:W339–W346CrossRef

Medema MH, Raaphorst R, Takano E Breitling R. (2012) Computational tools for the synthetic design of biochemical pathways. Nat Rev Microbiol 10:191–202

Medema MH, Cimermancic P, Sali A, Takano E, Fischbach MA (2014) A systematic computational analysis of biosynthetic gene cluster evolution: lessons for engineering biosynthesis. PLoS Comput Biol 10:e1004016CrossRef

Müller U, van Assema F, Gunsior M, Orf S, Kremer S, Schipper D, Wagemans A, Townsend CA, Sonke T, Bovenberg R, Wubbolts M (2006) Metabolic engineering of the E. coli l-phenylalanine pathway for the production of d-phenylglycine (d-Phg). Metab Eng 8:196–208CrossRef

Na D, Lee D (2010) RBSDesigner: software for designing synthetic ribosome binding sites that yields a desired level of protein expression. Bioinformatics 26:2633–2634CrossRef

Nevoigt E (2008) Progress in metabolic engineering of Saccharomyces cerevisiae. Microbiol Mol Biol Rev 72:379–412CrossRef

Nielsen J (2013) Production of biopharmaceutical proteins by yeast: advances through metabolic engineering. Bioengineered 4(4):207–211CrossRef

Osterlund T, Bordel S, Nielsen J (2015) Controllability analysis of transcriptional regulatory networks reveals circular control patterns among transcription factors. Integr Biol 7:560–568CrossRef

Otero JM, Cimini D, Patil KR, Poulsen SG, Olsson L, Nielsen J (2013) Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid Cell factory. PLoS ONE 8:1–10

Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496:528–532CrossRef

Partow S, Siewers V, Bjørn S, Nielsen J, Maury J (2010) Characterization of different promoters for designing a new expression vector in Saccharomyces cerevisiae. Yeast 27:955–964CrossRef

Payne T, Finnis C, Evans LR, Mead DJ, Avery SV, Archer DB, Sleep D (2008) Appl Environ Microbiol 74:7759–7766CrossRef

Pharkya P, Burgard AP Maranas CD (2004) OptStrain: a computational framework for redesign of microbial production systems. Genome Res 14: 2367–2376

Picotti P, Clement-Ziza M, Lam H, Campbell DS, Schmidt A, Deutsch EW, Rost H, Sun Z, Rinner O, Reiter L, Shen Q, Michaelson JJ, Frei A, Alberti S, Kusebauch U, Wollscheid B, Moritz RL, Beyer A, Aebersold R (2013) Complete mass spectrometric map of the yeast proteome applied to quantitative trait analysis. Nature 494:266–270CrossRef

Piirainen MA, de Ruijter JC, Koskela EV, Frey AD (2014) Glycoengineering of yeasts from the perspective of glycosylation efficiency. New Biotechnol 31(6):532–537CrossRef

Prather KLJ, Martin CH (2008) De novo biosynthetic pathways: rational design of microbial chemical factories. Curr Opin Biotechnol 19:468–474CrossRef

Rabinovich GA, van Kooyk Y, Cobb BA (2012) Glycobiology of immune responses. Ann N Y Acad Sci 1253:1–15CrossRef

Rapoport TA (2007) Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature 450:663–669CrossRef

Ravin NV, EldarovMA Kadnikov VV et al (2013) Genome sequence and analysis of methylotrophic yeast Hansenula polymorpha DL1. BMC Genom 14:837CrossRef

Robinson A, Hines V, Wittrup K (1994) Protein disulfide isomerase overexpression increases secretion of foreign proteins in Saccharomyces cerevisiae. Biotechnol (NY) 12:381–384CrossRef

Robson GD (2007) Exploitation of fungi. Cambridge University Press, Cambridge, UKCrossRef

Rodrigo G, Carrera J, Prather KJ, Jaramillo A (2008) DESHARKY: automatic design of metabolic pathways for optimal cell growth. Bioinformatics 24:2554–2556CrossRef

Sanchez BJ, Nielsen J (2015) Genome scale models of yeast: towards standardized evaluation and consistent omic integration. Integr Biol 7(8):846–858CrossRef

Sánchez C, Zhu L, Braña AF, Salas AP, Rohr J, Méndez C, Salas JA (2005) Combinatorial biosynthesis of antitumor indolocarbazole compounds. Proc Natl Acad Sci 102:461–466CrossRef

Schroder M (2007) The cellular response to protein unfolding stress. In: Robson GD, van West P, Gadd GM (eds) Exploitation of fungi. British mycological society symposium series, vol 26. Cambridge University Press, Cambridge, pp 117–139

Schröder M (2008) Engineering eukaryotic protein factories. Biotechnol Letters 30(2): 187–196

Shao Z, Rao G, Li C, Abil Z, Luo Y, Zhao H (2013) Refactoring the silent spectinabilin gene cluster using a plug-and-play scaffold. ACS Synth Biol 2:662–669CrossRef

Singh V (2014) Recent advancements in synthetic biology: current status and challenges. Gene 535:1–11CrossRef

Song Y, Choi MH, Park JN, Kim MW, Kim EJ, Kang HA, Kim JY (2007) Engineering of the yeast Yarrowia lipolytica for the production of glycoproteins lacking the outer-chain mannose residues of N-glycans. Appl Environ Microbiol 73:4446–4454CrossRef

Stephanopoulos G (2012) Synthetic biology and metabolic engineering. ACS Synth Biol 1:514–525CrossRef

Strahl-Bolsinger S, Gentzsch M, Tanner W (1999) Protein O-mannosylation. Biochim Biophys Acta 1426:297–307CrossRef

Swartz JR (2001) Advances in Escherichia coli production of therapeutic proteins. Curr Opin Biotechnol 12:195–201CrossRef

Temme K, Zhao D, Voigt CA (2012) Refactoring the nitrogen fixation gene cluster from Klebsiella oxytoca. Proc Natl Acad Sci 109:7085–7090CrossRef

Tyo KE, Liu Z, Magnusson Y, Petranovic D, Nielsen J (2014) Impact of protein uptake and degradation on recombinant protein secretion in yeast Applied Microbiology and Biotechnology 98(16):7149

Valkonen M, Penttilä M, Saloheimo M (2003) Effects of inactivation and constitutive expression of the unfolded-protein response pathway on protein production in the yeast Saccharomyces cerevisiae. Appl Environ Microbiol 69:2065–2072CrossRef

Van Ooyen AJ, Dekker P, Huang M, Olsthoorn MM, Jacobs DI, Colussi PA, Taron CH (2006) Heterologous protein production in the yeast Kluyveromyces lactis. FEMS Yeast Res 6:381–392CrossRef

Vogl T, Glieder A (2013) Regulation of Pichia pastoris promoters and its consequences for protein production. New Biotechnol 30:385–404CrossRef

Walsh G (2010) Biopharmaceutical benchmarks 2010. Nat Biotechnol 28:917–924CrossRef

Wriessnegger T, Pichler H (2013) Yeast metabolic engineering—targeting sterol metabolism and terpenoid formation. Prog Lipid Res 52:277–293CrossRef

Wu SG, He L, Wang Q, Tang YJ (2015) An ancient Chinese wisdom for metabolic engineering. Microb Cell Fact 14:39CrossRef

Yoshida H (2007) ER stress and diseases. FEBS J 274:630–658CrossRef

Zhang W, Zhao HL, Xue C, Xiong XH, Yao XQ, Li XY, Chen HP, Liu ZM (2006) Enhanced secretion of heterologous proteins in Pichia pastoris following overexpression of Saccharomyces cerevisiae chaperone proteins. Biotechnol Prog 22:1090–1095CrossRef

Zhu F, Zhong X, Hu M, Lu L, Deng Z, Liu T (2014) In vitro reconstitution of mevalonate pathway and targeted engineering of farnesene over production in Escherichia coli. Biotechnol Bioeng 111:1396–1405CrossRef

Title: Advances and Tools in Engineering Yeast for Pharmaceutical Production
Authors: Aravind Madhavan
Raveendran Sindhu
K. B. Arun
Ashok Pandey
Parameswaran Binod
Publisher: Springer Singapore
Book: Biosynthetic Technology and Environmental Challenges
Print ISBN: 978-981-10-7433-2

Electronic ISBN: 978-981-10-7434-9

Copyright Year: 2018
DOI: https://doi.org/10.1007/978-981-10-7434-9_3

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