A Distinct Aromatic Prenyltransferase Associated with the Futalosine Pathway

Abstract

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.

Menaquinone Biosynthesis: Biochemical and Structural Studies of Chorismate Dehydratase

“… In the next step, the radical SAM enzyme MqnE (SCO4494) catalyzes the transformation of 2 into aminofutalosine 3 . , Aminofutalosine 3 is then converted to compound 4 by aminofutalosine hydrolase (MqnB, SCO4327) or by a combination of aminofutalosine deaminase (SCO5662) and MqnB. − Cyclization of 4 , catalyzed by another radical SAM enzyme, MqnC (SCO4550), gives compound 5 , which is then converted to 5,8-dihydroxy-2-naphthoic acid 6 by MqnD (SCO4326). The genes likely to be involved in the conversion of 6 to menaquinone 9 have been identified, on the basis of frequent clustering with other Mqn genes and sequence similarity to proteins of closely related function in ubiquinone biosynthesis. , SCO4491 (MqnP) is likely to catalyze the prenylation reaction to give 7 ; SCO4490 (MqnL) and SCO4492 (MqnM) are likely to catalyze the decarboxylation, and SCO4556 (MqnG) is likely to catalyze the methylation reaction to give menaquinone 9 . In this paper, we report H/D exchange experiments, a pH–rate profile, and structural studies of the MqnA/3–hydroxybenzoic acid complex.…”

A multiplex approach of MS, 1D‐, and 2D‐NMR metabolomics in plant ontogeny: A case study on Clusia minor L. organs (leaf, flower, fruit, and seed)

“…Prenylated phenolic acids present novel functions such as in Humulus lupulus L. (hop) and Morus alba L. as cytotoxic and anti‐inflammatory agents 18,19 and have yet to be explored in Clusia . Thus, Clusia is a perfect research target for our interest in both plant lipids collected by bees 20–22 and prenylated aromatics, for example, in Hypericum 23–25 …”

“…Thus, Clusia is a perfect research target for our interest in both plant lipids collected by bees [20][21][22] and prenylated aromatics, for example, in Hypericum. [23][24][25] Clusia minor is a dioecious species traditionally used to treat pain and inflammation in sores and warts. Extracts from its leaves exhibit antioxidant, anti-inflammatory, and cytotoxic activities based on in vitro and in vivo studies.…”