Structure and biological evaluation of new cyclic and acyclic laxaphycin-A type peptides

Shared PKS modules in biosynthesis of synergistic laxaphycins

“…The 3-OHLeu 3 is conserved in 12-residue laxaphycins and 3-OHLeu 5 and OHAsn 8 are common in 12-residue laxaphycins (Table 1). Bornancin et al (2019) predicted that laxaphycin gene clusters should have FAAL and PKS modules to initiate biosynthesis, because the 11-residue acyclic acyclolaxaphycins have a break just before the Aoc and cyclization would be the last step of synthesis. Bornancin et al (2015) found acyclic 11-residue laxaphycin variants with a gap between the second and third amino acid in sequence starting with the Adc.…”

“…Cyclic lipopeptides are common among the cyanobacterial natural products and typically contain a single fatty acid as in laxaphycins (Galica et al, 2017) that confers membrane-disruptive properties (Humisto et al, 2019). Laxaphycin family peptides have been shown to be toxic to or inhibit the growth of multiple organisms and cell lines (Gerwick et al, 1989; Frankmölle et al, 1992b; Bonnard et al, 1997; MacMillan et al, 2002; Bonnard et al, 2007; Maru et al, 2010; Luo et al, 2014; Luo et al, 2015; Dussault et al, 2016; Cai et al, 2018; Bornancin et al, 2019). We observed antifungal activity of scytocyclamides towards A. flavus (Figure3, Table S3).…”

“…NRPS and PKS biosynthesis typically follow a co-linearity rule, where the genomic order of the catalytic domains corresponds to the order of the product structure (Guenzi et al, 1998; Callahan et al, 2009). The natural product family of laxaphycins are hypothesized to be produced by the PKS/NRPS hybrid pathway (Bornancin et al, 2015; Bornancin et al, 2019).…”

Assessment of the Chemical Diversity and Potential Toxicity of Benthic Cyanobacterial Blooms in the Lagoon of Moorea Island (French Polynesia)

“…This was particularly obvious for Anabaena sp.1 and L. majuscula. Anabaena sp.1 forms blooms that are apparently becoming increasingly frequent in coral reefs of many tropical and sub-tropical areas worldwide, such as in islands of Moorea (blooms reported in previous studies as A. torulosa) [22,24,25,27], Tahiti, Mayotte and La Réunion [22], where they periodically cover entire reefs. L. majuscula has a long history of observations in different parts of the world, including massive blooms as well as reports of toxicity causing skin irritations, such as in Australia and Mayotte Island [10,40].…”

“…This is, for example, the case in Moorea Island (French Polynesia), where benthic cyanobacterial proliferations have been often observed during the warm season over the two past decades, especially in coral habitats degraded by anthropogenic activities (e.g., coastal development, tourism, fishing) [22]. Previous studies on these proliferating cyanobacteria mainly focused on the characterization of newly described bioactive metabolites in the filamentous cyanobacteria Lyngbya majuscula and Anabaena torulosa [23][24][25][26][27]. To the best of our knowledge, no harmful events for humans associated with these benthic cyanobacterial blooms have been reported so far in Moorea Island.…”