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.
Puan
Kia-Joo
KJ
Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Group in Immunology, University of Iowa, EMRB 340F, Iowa City, IA 52242, USA.
Wang
Hong
H
Dairi
Tohru
T
Kuzuyama
Tomohisa
T
Morita
Craig T
CT
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