Evolutionary Relationships of Microbial Aromatic Prenyltransferases

Tobias Bonitz,Vikram Alva,Lutz Heide,Andrei N. Lupas,Orwah Saleh,Vladimir N. Uversky

doi:10.1371/journal.pone.0027336

Tobias Bonitz, Vikram Alva + Show 4 more

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https://doi.org/10.1371/journal.pone.0027336

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Abstract

The linkage of isoprenoid and aromatic moieties, catalyzed by aromatic prenyltransferases (PTases), leads to an impressive diversity of primary and secondary metabolites, including important pharmaceuticals and toxins. A few years ago, a hydroxynaphthalene PTase, NphB, featuring a novel ten-stranded β-barrel fold was identified in Streptomyces sp. strain CL190. This fold, termed the PT-barrel, is formed of five tandem ααββ structural repeats and remained exclusive to the NphB family until its recent discovery in the DMATS family of indole PTases. Members of these two families exist only in fungi and bacteria, and all of them appear to catalyze the prenylation of aromatic substrates involved in secondary metabolism. Sequence comparisons using PSI-BLAST do not yield matches between these two families, suggesting that they may have converged upon the same fold independently. However, we now provide evidence for a common ancestry for the NphB and DMATS families of PTases. We also identify sequence repeats that coincide with the structural repeats in proteins belonging to these two families. Therefore we propose that the PT-barrel arose by amplification of an ancestral ααββ module. In view of their homology and their similarities in structure and function, we propose to group the NphB and DMATS families together into a single superfamily, the PT-barrel superfamily.

Highlights

Aromatic prenyltransferases (PTases) catalyze the transfer of isoprenyl moieties to aromatic acceptor molecules, forming C-C bonds
To calculate the root mean square deviation (RMSD) and TMscores for the proteins included in this study, we used the TMalign server [20] with default parameters
To evaluate homology between PTases we used HHsearch [21], a sensitive remote homology detection method based on the pairwise comparison of profile hidden Markov models (HMMs)

Summary

Introduction

Aromatic prenyltransferases (PTases) catalyze the transfer of isoprenyl moieties to aromatic acceptor molecules, forming C-C bonds They are key enzymes in the biosynthesis of lipoquinones and of many secondary metabolites in plants, fungi and bacteria [1]. Aromatic PTases of lipoquinone biosynthesis are integral membrane proteins They contain an aspartate-rich motif (e.g. NDxxD) for binding of the prenyl diphosphate substrate via a Mg2+ ion, similar to the corresponding motif of farnesyl diphosphate synthase [2]. NphB was found to display a hitherto unobserved b-barrel fold which was termed the PT-barrel (Fig. 2; PDB 1ZB6). In silico structure predictions suggest that all these proteins adopt the PT-barrel fold Eleven of these enzymes have been investigated biochemically, and all of them catalyze the C-prenylation of aromatic compounds, i.e. phenols or phenazines. S1 (Supplementary Material) lists the references and accession numbers for all these enzymes and for all other proteins included in this study

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