New Opportunities by Synthetic Biology for Biopharmaceutical Production in Pichia Pastoris

Overview

Journal Curr Opin Biotechnol

Publisher Elsevier

Specialty Biotechnology

Date 2013 Mar 26

PMID 23522654

Citations 65

Authors

Thomas Vogl

Franz S Hartner

Anton Glieder

Affiliations

Soon will be listed here.

Abstract

Biopharmaceuticals are an integral part of modern medicine and pharmacy. Both, the development and the biotechnological production of biopharmaceuticals are highly cost-intensive and require suitable expression systems. In this review we discuss established and emerging tools for reengineering the methylotrophic yeast Pichia pastoris for biopharmaceutical production. Recent advancements of this industrial expression system through synthetic biology include synthetic promoters to avoid methanol induction and to fine-tune protein production. New platform strains and molecular cloning tools as well as in vivo glycoengineering to produce humanized glycoforms have made P. pastoris an important host for biopharmaceutical production.

Citing Articles

Beyond , Pharmaceutical Molecule Production in Cell-Free Systems and the Use of Noncanonical Amino Acids Therein.

Casteleijn M, Abendroth U, Zemella A, Walter R, Rashmi R, Haag R Chem Rev. 2025; 125(3):1303-1331.

PMID: 39841856 PMC: 11826901. DOI: 10.1021/acs.chemrev.4c00126.

Engineering for efficient production of recombinant proteins.

Yang S, Song L, Wang J, Zhao J, Tang H, Bao X Eng Microbiol. 2024; 4(1):100122.

PMID: 39628786 PMC: 11611019. DOI: 10.1016/j.engmic.2023.100122.

High-efficiency secretory expression and characterization of the recombinant type III human-like collagen in Pichia pastoris.

Xiang Z, Gong J, Shi J, Liu C, Li H, Su C Bioresour Bioprocess. 2024; 9(1):117.

PMID: 38647563 PMC: 10992891. DOI: 10.1186/s40643-022-00605-4.

as a Platform for Heterologous Expression of Enzymes Used for Industry.

Khlebodarova T, Bogacheva N, Zadorozhny A, Bryanskaya A, Vasilieva A, Chesnokov D Microorganisms. 2024; 12(2).

PMID: 38399750 PMC: 10892927. DOI: 10.3390/microorganisms12020346.

The advent of plant cells in bioreactors.

Verdu-Navarro F, Moreno-Cid J, Weiss J, Egea-Cortines M Front Plant Sci. 2023; 14:1310405.

PMID: 38148861 PMC: 10749943. DOI: 10.3389/fpls.2023.1310405.

References

Goodman M . Market watch: Sales of biologics to show robust growth through to 2013. Nat Rev Drug Discov. 2009; 8(11):837. DOI: 10.1038/nrd3040. View

Yadav V, De Mey M, Lim C, Ajikumar P, Stephanopoulos G . The future of metabolic engineering and synthetic biology: towards a systematic practice. Metab Eng. 2012; 14(3):233-41. PMC: 3615475. DOI: 10.1016/j.ymben.2012.02.001. View

Palmberger D, Klausberger M, Berger I, Grabherr R . MultiBac turns sweet. Bioengineered. 2012; 4(2):78-83. PMC: 3609625. DOI: 10.4161/bioe.22327. View

Hamilton S, Gerngross T . Glycosylation engineering in yeast: the advent of fully humanized yeast. Curr Opin Biotechnol. 2007; 18(5):387-92. DOI: 10.1016/j.copbio.2007.09.001. View

De Pourcq K, De Schutter K, Callewaert N . Engineering of glycosylation in yeast and other fungi: current state and perspectives. Appl Microbiol Biotechnol. 2010; 87(5):1617-31. DOI: 10.1007/s00253-010-2721-1. View

Gasser B, Prielhofer R, Marx H, Maurer M, Nocon J, Steiger M . Pichia pastoris: protein production host and model organism for biomedical research. Future Microbiol. 2013; 8(2):191-208. DOI: 10.2217/fmb.12.133. View

Ruth C, Glieder A . Perspectives on synthetic promoters for biocatalysis and biotransformation. Chembiochem. 2010; 11(6):761-5. DOI: 10.1002/cbic.200900761. View

Jacobs P, Ryckaert S, Geysens S, De Vusser K, Callewaert N, Contreras R . Pichia surface display: display of proteins on the surface of glycoengineered Pichia pastoris strains. Biotechnol Lett. 2008; 30(12):2173-81. DOI: 10.1007/s10529-008-9807-1. View

Li H, Sethuraman N, Stadheim T, Zha D, Prinz B, Ballew N . Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nat Biotechnol. 2006; 24(2):210-5. DOI: 10.1038/nbt1178. View

10.

Czlapinski J, Bertozzi C . Synthetic glycobiology: Exploits in the Golgi compartment. Curr Opin Chem Biol. 2006; 10(6):645-51. DOI: 10.1016/j.cbpa.2006.10.009. View

11.

Heyland J, Fu J, Blank L, Schmid A . Carbon metabolism limits recombinant protein production in Pichia pastoris. Biotechnol Bioeng. 2011; 108(8):1942-53. DOI: 10.1002/bit.23114. View

12.

Mattanovich D, Branduardi P, Dato L, Gasser B, Sauer M, Porro D . Recombinant protein production in yeasts. Methods Mol Biol. 2011; 824:329-58. DOI: 10.1007/978-1-61779-433-9_17. View

13.

Lin S, Houston-Cummings N, Prinz B, Moore R, Bobrowicz B, Davidson R . A novel fragment of antigen binding (Fab) surface display platform using glycoengineered Pichia pastoris. J Immunol Methods. 2011; 375(1-2):159-65. DOI: 10.1016/j.jim.2011.10.003. View

14.

Naatsaari L, Mistlberger B, Ruth C, Hajek T, Hartner F, Glieder A . Deletion of the Pichia pastoris KU70 homologue facilitates platform strain generation for gene expression and synthetic biology. PLoS One. 2012; 7(6):e39720. PMC: 3387205. DOI: 10.1371/journal.pone.0039720. View

15.

Jahic M, Veide A, Charoenrat T, Teeri T, Enfors S . Process technology for production and recovery of heterologous proteins with Pichia pastoris. Biotechnol Prog. 2006; 22(6):1465-73. DOI: 10.1021/bp060171t. View

16.

Pan R, Zhang J, Shen W, Tao Z, Li S, Yan X . Sequential deletion of Pichia pastoris genes by a self-excisable cassette. FEMS Yeast Res. 2011; 11(3):292-8. DOI: 10.1111/j.1567-1364.2011.00716.x. View

17.

Nett J, Gerngross T . Cloning and disruption of the PpURA5 gene and construction of a set of integration vectors for the stable genetic modification of Pichia pastoris. Yeast. 2003; 20(15):1279-90. DOI: 10.1002/yea.1049. View

18.

Walsh G . Post-translational modifications of protein biopharmaceuticals. Drug Discov Today. 2010; 15(17-18):773-80. DOI: 10.1016/j.drudis.2010.06.009. View

19.

Nett J, Stadheim T, Li H, Bobrowicz P, Hamilton S, Davidson R . A combinatorial genetic library approach to target heterologous glycosylation enzymes to the endoplasmic reticulum or the Golgi apparatus of Pichia pastoris. Yeast. 2011; 28(3):237-52. DOI: 10.1002/yea.1835. View

20.

Nett J, Gomathinayagam S, Hamilton S, Gong B, Davidson R, Du M . Optimization of erythropoietin production with controlled glycosylation-PEGylated erythropoietin produced in glycoengineered Pichia pastoris. J Biotechnol. 2011; 157(1):198-206. DOI: 10.1016/j.jbiotec.2011.11.002. View