RRC ID 35483
著者 Kim J, Copley SD.
タイトル Inhibitory cross-talk upon introduction of a new metabolic pathway into an existing metabolic network.
ジャーナル Proc Natl Acad Sci U S A
Abstract Evolution or engineering of novel metabolic pathways can endow microbes with new abilities to degrade anthropogenic pollutants or synthesize valuable chemicals. Most studies of the evolution of new pathways have focused on the origins and quality of function of the enzymes involved. However, there is an additional layer of complexity that has received less attention. Introduction of a novel pathway into an existing metabolic network can result in inhibitory cross-talk due to adventitious interactions between metabolites and macromolecules that have not previously encountered one another. Here, we report a thorough examination of inhibitory cross-talk between a novel metabolic pathway for synthesis of pyridoxal 5'-phosphate and the existing metabolic network of Escherichia coli. We demonstrate multiple problematic interactions, including (i) interference by metabolites in the novel pathway with metabolic processes in the existing network, (ii) interference by metabolites in the existing network with the function of the novel pathway, and (iii) diversion of metabolites from the novel pathway by promiscuous activities of enzymes in the existing metabolic network. Identification of the mechanisms of inhibitory cross-talk can reveal the types of adaptations that must occur to enhance the performance of a novel metabolic pathway as well as the fitness of the microbial host. These findings have important implications for evolutionary studies of the emergence of novel pathways in nature as well as genetic engineering of microbes for "green" manufacturing processes.
巻・号 109(42)
ページ E2856-64
公開日 2012-10-16
DOI 10.1073/pnas.1208509109
PII 1208509109
PMID 22984162
PMC PMC3479479
MeSH Escherichia coli / metabolism* Escherichia coli Proteins / metabolism Evolution, Molecular* Genetic Engineering / methods* Metabolic Networks and Pathways / genetics* Metabolic Networks and Pathways / physiology Molecular Structure Pyridoxal Phosphate / biosynthesis* Pyruvates Synthetic Biology / methods*
IF 9.412
引用数 42
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
原核生物(大腸菌) ME9062(BW25113) Keio collection ASKA collection