Novel enzymology in futalosine-dependent menaquinone biosynthesis

Chorismate- and isochorismate converting enzymes: versatile catalysts acting on an important metabolic node

“…E. coli. 6,45 SEPHCHC synthases require thiamine diphosphate (ThDP) as a cofactor and elucidation of different threedimensional structures has indicated that MenD enzymes are magnesium (as in MST enzymes Section 4) or manganese dependent. 91,102,103 Product formation is suggested to proceed via two sequential half-reactions including two covalent intermediates (Scheme 4).…”

“…Genome network analyses indicate that chorismate dehydratases are involved in the biosynthesis of further natural products. 6 The only structurally and mechanistically characterised member to date is MqnA from D. radiodurans; the formation of the product 3-enoylpyruvyl benzoate (31) from chorismate was first shown for MqnA from Thermus thermophilus HB8. 46,110…”

“…§ Rather than providing an exhaustive compilation of original experiments, we aimed to prepare a general overview serving as a starting point for research into the field and as a complement to a wealth of prior subfamily-and subtopic-specific reviews. [6][7][8][9][10][11][12][13] In addition, recent advances in the field and their potential influence on the understanding of chorismate-converting enzymes in general are highlighted, followed by a brief overview of novel chorismate-derived natural products and biocatalytic applications of chorismate-converting enzymes.…”

Advances in bacterial pathways for the biosynthesis of ubiquinone

“…The classical MK pathway has only two steps related to the UQ pathway: the prenylation step catalyzed by the prenyltransferase MenA (homologous to UbiA) and the methylation of the aromatic ring catalyzed by the literally shared enzyme MenG/UbiE. The characterized mqnA-E genes are specific to the futalosine pathway81 , but the still putative MqnP, MqnL, MqnM, and UbiE/MenG have homologs in the UQ pathway…”

Antibacterial Strategy against H. pylori: Inhibition of the Radical SAM Enzyme MqnE in Menaquinone Biosynthesis

“…5 Menaquinone biosynthesis is therefore an attractive target for antibiotic development, 6 and inhibitors against Gram-positive organisms such as Mycobacterium tuberculosis and Staphylococcus aureus have been identified. 7 The recent discovery of a new, futalosine-dependent, menaquinone biosynthesis pathway has presented new opportunities for antibacterial development 8,9 because important human pathogens including Helicobacter pylori (causes gastric ulcers and cancer), Campylobacter jejuni (causes diarrhea), Chlamydia strains (cause urethritis and respiratory tract infections), and Spirochetes (cause syphilis and Lyme disease) utilize this pathway. 10 The absence of this pathway in humans and in most of the human gut bacteria potentially provides the required selectivity for targeting this pathway without affecting the commensal bacteria.…”