Biosynthesis, Regulation and Export of Lasso Peptides - Lasso Peptides: Bacterial Strategies to Make and Maintain Bioactive Entangled Scaffolds - page 82

Fig. 4.2 Conserved motifs presented in B and C proteins. (With permission from Hegemann et al.
2014 )

recent reports analysed the sequence motifs in all functional maturation enzymes
(Maksimov et al. 2012 ; Hegemann et al. 2013b ) using the MEME algorithm (Bailey
et al. 2009 ). Two motifs were found for the B proteins (Fig. 4.2 ). LarB1 displays
the LDXXXXRYFXL motif that is located at the N-terminal region of full-length
B proteins, despite low overall sequence similarity. This suggests that they would
perform the same function, i.e. the ATPase activity. Alternatively, LarB1 would in-
teract with LarB2 or LarC and would display a structural role. Similarly, PqqD was
found to interact with PqqC and PqqE during PQQ biosynthesis (Toyama et al. 2007 ;
Wecksler et al. 2010 ). The exact function of LarB1 awaits in vitro characterization.
Nevertheless, it is conceivable that LarB1/B2/C would form a three-partner complex
analogous to MccJ25 synthetase. Such split-B systems are encoded in numerous
putative lasso peptide clusters. Actinobacteria seem to have higher occurrence of
such systems than proteobacteria, inferring different evolutionary scenarios in both
phyla. The modularity of B proteins may offer opportunity for combinatorial bio-
synthesis to generate novel lasso peptides. To date, lariatin and sviceucin are the two
confirmed lasso peptide family members synthesized by functional split-B enzymes
(Ducasse et al. 2012a ; Inokoshi et al. 2012 ). More functional split-B biosynthetic
enzymes need to be identified for deeper biochemical studies.

4.1.2 Role of Leader Peptides

Nearly all precursor peptides of RiPPs contain N-terminal leader peptide exten-
sions of various sizes and sequences (Oman and van der Donk 2010 ), except