Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli

• Published in: Science (American Association for the Advancement of Science) Vol. 330; no. 6000; pp. 70 - 74
• Main Authors: Ajikumar, Parayil Kumaran, Xiao, Wen-Hai, Tyo, Keith E. J., Wang, Yong, Simeon, Fritz, Leonard, Effendi, Mucha, Oliver, Phon, Too Heng, Pfeifer, Blaine, Stephanopoulos, Gregory
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.10.2010; The American Association for the Advancement of Science
• Subjects: Alkenes - metabolism; Biochemistry; Bioreactors; Biosynthesis; Cellular metabolism; Chemical engineering; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Diterpenes - metabolism; Drugs; E coli; Enzymes; Erythritol - analogs & derivatives; Erythritol - metabolism; Escherichia coli; Escherichia coli K12 - enzymology; Escherichia coli K12 - genetics; Escherichia coli K12 - metabolism; Farnesyltranstransferase - genetics; Farnesyltranstransferase - metabolism; Fermentation; Genetic Engineering; Hemiterpenes - metabolism; Indoles; Indoles - metabolism; Isomerases - genetics; Isomerases - metabolism; Metabolic Networks and Pathways - genetics; Metabolomics; Modular; Modules; NADPH-Ferrihemoprotein Reductase - genetics; NADPH-Ferrihemoprotein Reductase - metabolism; Operons; Optimization; Organophosphorus Compounds - metabolism; Oxidation-Reduction; Pacific yew; Paclitaxel - biosynthesis; Pathways; Pharmacology; Plasmids; Recombinant Fusion Proteins - metabolism; Searching; Streams; Sugar Phosphates - metabolism; Taxoids - metabolism; Taxol; Taxus - enzymology; Taxus brevifolia; Terpenes - metabolism; Terpenoids

Taxol (paclitaxel) is a potent anticancer drug first isolated from the Taxus brevifolia Pacific yew tree. Currently, cost-efficient production of Taxol and its analogs remains limited. Here, we report a multivariate-modular approach to metabolic-pathway engineering that succeeded in increasing titer...