A tryptophan prenyltransferase with broad substrate tolerance from bacillus subtilis subsp. Natto

Bacillus subtilis subsp. natto secretes the ComX_natto pheromone as a quorum-sensing pheromone to produce poly-γ-glutamate for biofilm formation. The amino-acid sequence of the pheromone is Lys-Trp-Pro-Pro-Ile-Glu, and the tryptophan residue is post-translationally modified with a farnesyl group to form a tricyclic scaffold. Unlike other Bacillus ComX pheromones, the tryptophan residue is distant from the C-terminal end of the precursor peptide ComX_natto. Here, we report the functional analysis of ComQ_natto, which catalyzes a unique farnesyl-transfer reaction. ComQ_natto recognizes not only full-length ComX_natto but also N-and/or C-terminal truncated ComX_natto analogues and even a single tryptophan for modification with a farnesyl group in vitro. These results, together with the calculated kinetic parameters, suggest that ComQ_natto does not require a leader sequence for substrate recognition and is a promising enzyme with broad substrate tolerance for the synthesis of various prenylated tryptophan derivatives.