MOLECULAR-CLONING OF THE HAEMOPHILUS-INFLUENZAE GMHA (LPCA) GENE ENCODING A PHOSPHOHEPTOSE ISOMERASE REQUIRED FOR LIPOOLIGOSACCHARIDE BIOSYNTHESIS

We have determined that gene HI#1181 of Haemophilus influenzae is a ho molog of Escherichia coli gmhA (previously designated IpcA) (J. S. Bro oke and M. A. Valvano, J. Biol. Chem. 271:3608-3614, 1996), which enco des a phosphoheptose isomerase catalyzing the first step of the biosyn thesis of ADP-L-glycero-D-manno-heptose. Mutations in this gene are as sociated with a heptoseless core lipopolysaccharide which determines a n increased outer membrane permeability to hydrophobic compounds. The cloned H influenzae gmhA restored the synthesis of a complete core in the gmhA-deleted E. coli strain chi 711. Amino acid sequence compariso ns of the GmhA proteins of E. coli and H. influenzae with other protei ns in the databases revealed the existence of a novel family of phosph osugar aldo-keto isomerases.