A Distinct Aromatic Prenyltransferase Associated with the Futalosine Pathway

Menaquinone (MK) is an electron carrier molecule essential for respiration in most Gram positive bacteria. A crucial step in MK biosynthesis involves the prenylation of an aromatic molecule, catalyzed by integral membrane prenyltransferases of the UbiA (4‐hydroxybenzoate oligoprenyltransferase) superfamily. In the classical MK biosynthetic pathway, the prenyltransferase responsible is MenA (1,4‐dihydroxy‐2‐naphthoate octaprenyltransferase). Recently, an alternative pathway for formation of MK, the so‐called futalosine pathway, has been described in certain micro‐organisms. Until now, five soluble enzymes (MqnA‐MqnE) have been identified in the first steps. In this study, the genes annotated as ubiA from T. thermophilus and S. lividans were cloned, expressed and investigated for prenylation activity. The integral membrane proteins possess neither UbiA nor MenA activity and represent a distinct class of prenyltransferases associated with the futalosine pathway that we term MqnP. We identify a critical residue within a highly conserved Asp‐rich motif that serves to distinguish between members of the UbiA superfamily. A number of microorganisms, including several prominent human pathogens, utilize futalosine as an intermediate in the biosynthesis of the electron carrier menaquinone. A crucial step in synthesis of this lipophilic molecule involves the prenylation of an aromatic moiety. Here we analyse relevant Thermus thermophilus and Streptomyces lividans gene products corresponding to aromatic prenyltransferases and show that these integral membrane enzymes segregate into a distinct class of the UbiA superfamily.