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Inverse metabolic engineering: A strategy for directed genetic engineering of useful phenotypes
Author(s) -
Bailey James E.,
Sburlati Adriana,
Hatzimanikatis Vassily,
Lee Kelvin,
Renner Wolfgang A.,
Tsai Philip S.
Publication year - 2002
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.10441
Subject(s) - metabolic engineering , phenotype , bottleneck , synthetic biology , computational biology , systems biology , organism , metabolic pathway , biochemical engineering , biology , limiting , protein engineering , inverse , genome engineering , model organism , computer science , enzyme , genetics , genome , biochemistry , engineering , gene , mathematics , embedded system , mechanical engineering , cas9 , geometry
The classical method of metabolic engineering, identifying a rate‐determining step in a pathway and alleviating the bottleneck by enzyme overexpression, has motivated much research but has enjoyed only limited practical success. Intervention of other limiting steps, of counter‐balancing regulation, and of unknown coupled pathways often confounds this direct approach. Here the concept of inverse metabolic engineering is codified and its application is illustrated with several examples. Inverse metabolic engineering means the elucidation of a metabolic engineering strategy by: first, identifying, constructing, or calculating a desired phenotype; second, determining the genetic or the particular environmental factors conferring that phenotype; and third, endowing that phenotype on another strain or organism by directed genetic or environmental manipulation. This paradigm has been successfully applied in several contexts, including elimination of growth factor requirements in mammalian cell culture and increasing the energetic efficiency of microaerobic bacterial respiration. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 568–579, 2002.