Trichormamides C and D, antiproliferative cyclic lipopeptides from the cultured freshwater cyanobacterium cf. Oscillatoria sp. UIC 10045

Abstract

Extract from the cultured freshwater cf. Oscillatoria sp. UIC 10045 showed antiproliferative activity against HT-29 cell line. Bioassay-guided fractionation led to the isolation of two new cyclic lipopeptides, named trichormamides C (1) and D (2). The planar structures were determined by combined analyses of HRESIMS, Q-TOF ESIMS/MS, and 1D and 2D NMR spectra. The absolute configurations of the amino acid residues were assigned by the advanced Marfey’s analysis after partial and complete acid hydrolysis. Trichormamides C (1) is a cyclic undecapeptide and D (2) is a cyclic dodecapeptide, both containing a lipophilic β-aminodecanoic acid residue. Trichormamide C (1) displayed antiproliferative activities against HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 1.7 and 1.0 µM, respectively, as well as anti-Mycobacterium tuberculosis activity with MIC value of 23.8 µg/mL (17.3 µM). Trichormamide D (2) was found to be less potent against both HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 11.5 and 11.7 µM, respectively.

Shared PKS Module in Biosynthesis of Synergistic Laxaphycins

“…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 , 2007 ; MacMillan et al, 2002 ; Maru et al, 2010 ; Luo et al, 2014 , 2015 ; Dussault et al, 2016 ; Cai et al, 2018 ; Bornancin et al, 2019 ). We observed antifungal activity of scytocyclamides toward A. flavus ( Figure 3 and Supplementary Table S4 ).…”

“…Laxaphycins are cyanobacterial cyclic lipopeptides that fall in two distinct structural macrocycles consisting of either 11 amino acids (known as A-type laxaphycins) or 12 amino acids (known as B-type laxaphycins) (Frankmölle et al, 1992a;Luo et al, 2015). Both types include β-aminooctanoic acid (Aoa) or β-aminodecanoic acid (Ada) ( Table 1).…”

Isolation and Synthesis of Laxaphycin B-Type Peptides: A Case Study and Clues to Their Biosynthesis

“…Oscillatoria sp. [ 12 ] express laxaphycins B, B2, B3, and D, lobocyclamides B and C, and trichormamides B and C. Furthermore a Lyngbya sp. strain produces lyngbyacyclamides A and B [ 13 ] ( Figure 1 ).…”

Shared PKS modules in biosynthesis of synergistic laxaphycins

“…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).…”