Membrane transporter engineering in industrial biotechnology and whole cell biocatalysis

被引:155
作者
Kell, Douglas B. [1 ,2 ,3 ]
Swainston, Neil [2 ,3 ,4 ]
Pir, Pinar [5 ,6 ]
Oliver, Stephen G. [5 ,6 ]
机构
[1] Univ Manchester, Sch Chem, Manchester M1 7DN, Lancs, England
[2] Univ Manchester, Manchester Inst Biotechnol, Manchester M1 7DN, Lancs, England
[3] Univ Manchester, Ctr Synthet Biol Fine & Special Chem SYNBIOCHEM, Manchester M1 7DN, Lancs, England
[4] Univ Manchester, Sch Comp Sci, Manchester M13 9PL, Lancs, England
[5] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge CB2 1GA, England
[6] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
基金
英国生物技术与生命科学研究理事会;
关键词
drug transporters; biotechnology; stress tolerance; flux improvements; GWAS; MAJOR FACILITATOR SUPERFAMILY; ORGANIC-SOLVENT TOLERANCE; ESCHERICHIA-COLI; MULTIDRUG TRANSPORTER; SYSTEMS BIOLOGY; EFFLUX PUMP; PHARMACEUTICAL DRUGS; DIRECTED EVOLUTION; METABOLIC NETWORK; MEDIATED UPTAKE;
D O I
10.1016/j.tibtech.2015.02.001
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Because they mainly do not involve chemical changes, membrane transporters have been a Cinderella subject in the biotechnology of small molecule production, but this is a serious oversight. Influx transporters contribute significantly to the flux towards product, and efflux transporters ensure the accumulation of product in the much greater extracellular space of fermentors. Programmes for improving biotechnological processes might therefore give greater consideration to transporters than may have been commonplace. Strategies for identifying important transporters include expression profiling, genome-wide knockout studies, stress-based selection, and the use of inhibitors. In addition, modern methods of directed evolution and synthetic biology, especially those effecting changes in energy coupling, offer huge opportunities for increasing the flux towards extracellular product formation by transporter engineering.
引用
收藏
页码:237 / 246
页数:10
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