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B6db references: 20142041

type Journal Article
authors Johannes TW, DeSieno MA, Griffin BM, Thomas PM, Kelleher NL, Metcalf WW, Zhao H.
title Deciphering the late biosynthetic steps of antimalarial compound FR-900098.
journal Chemistry & biology
Activity frbh
Family frbh
sel selected
ui 20142041
year (2010)
volume 17
number 1
pages 57-64
abstract FR-900098 is a potent chemotherapeutic agent for the treatment of malaria. Here we report the heterologous production of this compound in Escherichia coli by reconstructing the entire biosynthetic pathway using a three-plasmid system. Based on this system, whole-cell feeding assays in combination with in vitro enzymatic activity assays reveal an unusual functional role of nucleotide conjugation and lead to the complete elucidation of the previously unassigned late biosynthetic steps. These studies also suggest a biosynthetic route to a second phosphonate antibiotic, FR-33289. A thorough understanding of the FR-900098 biosynthetic pathway now opens possibilities for metabolic engineering in E. coli to increase production of the antimalarial antibiotic and combinatorial biosynthesis to generate novel derivatives of FR-900098.

last changed 2018/03/27 10:10

B6db references