Metabolic engineering for microbial production of shikimic acid

被引:202
作者
Krämer, M [1 ]
Bongaerts, J [1 ]
Bovenberg, R [1 ]
Kremer, S [1 ]
Müller, U [1 ]
Orf, S [1 ]
Wubbolts, M [1 ]
Raeven, L [1 ]
机构
[1] DSM Biotech GmbH, D-52428 Julich, Germany
关键词
shikimic acid; shikimate; shikmate-3-phosphate; quinic acid; aromatic amino acid pathway; PEP; E4P; dehydroshikimic acid; dehydroshikimate; DHS;
D O I
10.1016/j.ymben.2003.09.001
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
Shikimic acid is a high valued compound used as a key starting material for the synthesis of the neuramidase inhibitor GS4104, which was developed under the name Tamiflu(R) for treatment of antiviral infections. An excellent alternative to the isolation of shikimic acid from fruits of the Illicium plant is the fermentative production by metabolic engineered microorganisms. Fermentative production of shikimic acid was most successfully carried out by rational designed Escherichia coli strains by blocking the aromatic amino acid pathway after the production of shikimic acid. An alternative is to produce shikimic acid as a result of dephosphorylation of shikimate-3-phosphate. Engineering the uptake of carbon, the regulatory circuits, central metabolism and the common aromatic pathway including shikimic acid import that have all been targeted to effect higher productivities and lower by-product formation are discussed. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:277 / 283
页数:7
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