Abstract
Background: Process development involving system metabolic engineering and bioprocess engineering has become one of the major thrust for the development of therapeutic proteins or enzymes. Pichia pastoris has emerged as a prominent host for the production of therapeutic protein or enzymes. Regardless of producing high protein titers, various cellular and process level bottlenecks restrict the expression of recombinant proteins in P. pastoris.
Result and Conclusion: In the present review, we have summarized the recent developments in the expression of foreign proteins in P. pastoris. Further, we have discussed various cellular engineering strategies which include codon optimization, pathway engineering, signal peptide processing, development of protease deficient strain and glyco-engineered strains for the high yield protein secretion of recombinant protein. Bioprocess development of recombinant proteins in large-scale bioreactor including medium optimization, optimum feeding strategy and co-substrate feeding in fed-batch as well as continuous cultivation have been described. The recent advances in system and synthetic biology studies including metabolic flux analysis in understanding the phenotypic characteristics of recombinant Pichia and genome editing with CRISPR-CAS system have also been summarized.
Keywords: Pichia pastoris, recombinant proteins, metabolic engineering, chaperones, glycoengineering, fed-batch and continuous cultivation.
Graphical Abstract
Current Pharmaceutical Biotechnology
Title:Gene and process level modulation to overcome the bottlenecks of recombinant proteins expression in Pichia pastoris
Volume: 18 Issue: 15
Author(s): Ashish A. Prabhu, Bibari Boro, Biju Bharali, Shuchishloka Chakraborty and Veeranki V. Dasu*
Affiliation:
- Biochemical Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam,India
Keywords: Pichia pastoris, recombinant proteins, metabolic engineering, chaperones, glycoengineering, fed-batch and continuous cultivation.
Abstract: Background: Process development involving system metabolic engineering and bioprocess engineering has become one of the major thrust for the development of therapeutic proteins or enzymes. Pichia pastoris has emerged as a prominent host for the production of therapeutic protein or enzymes. Regardless of producing high protein titers, various cellular and process level bottlenecks restrict the expression of recombinant proteins in P. pastoris.
Result and Conclusion: In the present review, we have summarized the recent developments in the expression of foreign proteins in P. pastoris. Further, we have discussed various cellular engineering strategies which include codon optimization, pathway engineering, signal peptide processing, development of protease deficient strain and glyco-engineered strains for the high yield protein secretion of recombinant protein. Bioprocess development of recombinant proteins in large-scale bioreactor including medium optimization, optimum feeding strategy and co-substrate feeding in fed-batch as well as continuous cultivation have been described. The recent advances in system and synthetic biology studies including metabolic flux analysis in understanding the phenotypic characteristics of recombinant Pichia and genome editing with CRISPR-CAS system have also been summarized.
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Cite this article as:
Prabhu A. Ashish , Boro Bibari, Bharali Biju , Chakraborty Shuchishloka and Dasu V. Veeranki *, Gene and process level modulation to overcome the bottlenecks of recombinant proteins expression in Pichia pastoris, Current Pharmaceutical Biotechnology 2017; 18 (15) . https://dx.doi.org/10.2174/1389201019666180329112827
DOI https://dx.doi.org/10.2174/1389201019666180329112827 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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