The deoxyxylulose phosphate pathway of isoprenoid biosynthesis. Discovery and function of the ispDEFGH genes and their cognate enzymes
F. Rohdich, S. Hecht, A. Bacher, and W. Eisenreich
Lehrstuhl für Organische Chemie und Biochemie,
Technische Universität München, Lichtenbergstraße 4,
D-85747 Garching, Germany
Abstract: Isopentenyl diphosphate (IPP) and dimethylallyl
diphosphate (DMAPP) serve as the universal precursors for the biosynthesis
of terpenes. Besides the well-known mevalonate pathway, a second biosynthetic
pathway conducive to IPP and DMAPP via 1-deoxy-D-xylulose-5-phosphate
and 2C-methyl-D-erythritol-4-phosphate
has been discovered recently in plants and certain eubacteria. 2C-Methyl-D-erythritol-4-phosphate,
the first committed intermediate of the deoxyxylulose phosphate pathway,
is converted into 2C-methyl-D-erythritol
2,4-cyclodiphosphate by the catalytic action of three enzymes specified
by the ispDEF genes. The cyclic diphosphate is reductively
opened by the IspG protein affording 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate.
This compound can be converted into IPP as well as DMAPP by the catalytic
action of IspH protein. The enzymes of this pathway are potential targets
for novel antibacterial, antimalarial, and herbicide agents.
*Pure Appl.Chem. 75,
141�419 (2003). An issue of reviews and research papers based on
lectures presented at the 23rd IUPAC International Symposium on the
Chemistry of Natural Products, Florence, Italy, 28 July � 2 August 2002.
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