fldA is an essential gene required in the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis.
Although flavodoxin I is indispensable for Escherichia coli growth, the exact pathway(s) where flavodoxin I is essential has not been identified. We performed transposon mutagenesis of the flavodoxin I gene, fldA, in an E. coli strain that expressed mevalonate pathway enzymes and that had a point mutation in the lytB gene of the MEP pathway resulting in the accumulation of (E)-4-hydroxy-3-methylbutyl-2-enyl pyrophosphate (HMBPP). Disruption of fldA abrogated mevalonate-independent growth and dramatically decreased HMBPP levels. The fldA- mutant grew with mevalonate indicating that the essential role of flavodoxin I under aerobic conditions is in the MEP pathway. Growth was restored by fldA complementation. Since GcpE (which synthesizes HMBPP) and LytB are iron-sulfur enzymes that require a reducing system for their activity, we propose that flavodoxin is essential for GcpE and possibly LytB activity. Thus, the essential role for flavodoxin I in E. coli is in the MEP pathway for isoprenoid biosynthesis.
Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Group in Immunology, University of Iowa, EMRB 340F, Iowa City, IA 52242, USA.
Kia-Joo
KJ
Puan
Hong
H
Wang
Tohru
T
Dairi
Tomohisa
T
Kuzuyama
Craig T
CT
Morita
D019943:Amino Acid Substitution; D001224:Aspartic Acid / Q000235:genetics; D004896:Erythritol / Q000031:analogs & derivatives* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology*; D005418:Flavodoxin / Q000235:genetics* / Q000378:metabolism; D020043:Genes, Essential; D005816:Genetic Complementation Test; D005998:Glycine / Q000235:genetics; D016296:Mutagenesis; D013403:Sugar Phosphates / Q000378:metabolism*; D013729:Terpenes / Q000378:metabolism*
C114232:2-C-methylerythritol 4-phosphate; D029968:Escherichia coli Proteins; D005418:Flavodoxin; D013403:Sugar Phosphates; D013729:Terpenes; C100447:flavodoxin 1; D001224:Aspartic Acid; D004896:Erythritol; D005998:Glycine