a gene optimization strategy that enhances production of fully functional p-glycoprotein in pichia pastoris一个基因优化策略,增强了功能齐全的pastoris 22在毕赤酵母的生产.pdfVIP
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a gene optimization strategy that enhances production of fully functional p-glycoprotein in pichia pastoris一个基因优化策略,增强了功能齐全的pastoris 22在毕赤酵母的生产
A Gene Optimization Strategy that Enhances Production
of Fully Functional P-Glycoprotein in Pichia pastoris
1.¤ 1. 2 2,3 1
Jiangping Bai , Douglas J. Swartz , Irina I. Protasevich , Christie G. Brouillette , Patina M. Harrell ,
1 4 4 5 5
Ellen Hildebrandt , Brigitte Gasser , Diethard Mattanovich , Andrew Ward , Geoffrey Chang , Ina L.
Urbatsch1*
1 Department of Cell Biology and Biochemistry, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
of America, 2 Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Center for Biophysical Sciences and
Engineering, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 4 Department of Biotechnology, University of Natural Resources and
Life Sciences, Vienna, Austria, 5 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America
Abstract
Background: Structural and biochemical studies of mammalian membrane proteins remain hampered by inefficient
production of pure protein. We explored codon optimization based on highly expressed Pichia pastoris genes to enhance
co-translational folding and production of P-glycoprotein (Pgp), an ATP-dependent drug efflux pump involved in multidrug
resistance of cancers.
Methodology/Principal Findings: Codon-optimized ‘‘Opti-Pgp’’ and wild-type Pgp, identical in primary protein sequence,
were rigorously analyzed for differences in function or solu
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