An alternative menaquinone biosynthetic pathway operating in microorganisms.
In microorganisms, menaquinone is an obligatory component of the electron-transfer pathway. It is derived from chorismate by seven enzymes in Escherichia coli. However, a bioinformatic analysis of whole genome sequences has suggested that some microorganisms, including pathogenic species such as Helicobacter pylori and Campylobacter jejuni, do not have orthologs of the men genes, even though they synthesize menaquinone. We deduced the outline of this alternative pathway in a nonpathogenic strain of Streptomyces by bioinformatic screening, gene knockouts, shotgun cloning with isolated mutants, and in vitro studies with recombinant enzymes. As humans and commensal intestinal bacteria, including lactobacilli, lack this pathway, it represents an attractive target for the development of chemotherapeutics.
Hiratsuka
Tomoshige
T
Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan.
Furihata
Kazuo
K
Ishikawa
Jun
J
Yamashita
Haruyuki
H
Itoh
Nobuya
N
Seto
Haruo
H
Dairi
Tohru
T
D001105:Archaea / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D001419:Bacteria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics; D016123:Campylobacter jejuni / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D002827:Chorismic Acid / Q000378:metabolism; D003001:Cloning, Molecular; D019295:Computational Biology; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009705:Nucleosides / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D048372:Streptomyces coelicolor / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D016963:Thermus thermophilus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D024482:Vitamin K 2 / Q000378:metabolism*
D004798:Enzymes; D009705:Nucleosides; D011994:Recombinant Proteins; C122040:futalosine; D024482:Vitamin K 2; D002827:Chorismic Acid