Evolutionary relationships of microbial aromatic prenyltransferases

Area of Science:

• Biochemistry
• Structural Biology
• Evolutionary Biology

Background:

• Aromatic prenyltransferases (PTases) are crucial enzymes catalyzing the linkage of isoprenoid and aromatic moieties.
• This enzymatic activity generates diverse primary and secondary metabolites, including pharmaceuticals and toxins.
• A novel ten-stranded β-barrel fold, the PT-barrel, was identified in NphB from Streptomyces sp. strain CL190.

Purpose of the Study:

• To investigate the evolutionary relationship between the NphB and DMATS families of prenyltransferases.
• To determine if the PT-barrel fold arose from independent convergent evolution or a common ancestor.
• To propose a unified classification for these enzyme families based on structural and functional evidence.

Main Methods:

• Sequence comparisons using Position-Specific Iterated BLAST (PSI-BLAST).
• Analysis of structural repeats within the NphB and DMATS protein families.
• Comparative analysis of protein structure and function.

Main Results:

• Evidence for common ancestry between the NphB and DMATS PTase families was established.
• Sequence repeats were identified that correspond to the structural repeats within the PT-barrel fold.
• The PT-barrel fold is proposed to have evolved through the amplification of an ancestral ααββ module.

Conclusions:

• The NphB and DMATS families share a common evolutionary origin, refuting independent convergence for the PT-barrel fold.
• The PT-barrel fold likely arose from the duplication and amplification of a smaller structural unit.
• A new superfamily, the PT-barrel superfamily, is proposed to encompass both the NphB and DMATS families due to their homology and shared characteristics.