Structure and Biosynthesis of Desmamides A–C, Lipoglycopeptides from the Endophytic Cyanobacterium Desmonostoc muscorum LEGE 12446

Abstract

Certain cyanobacteria of the secondary metabolite-rich order Nostocales can establish permanent symbioses with a large number of cycads, by accumulating in their coralloid roots and shifting their metabolism to dinitrogen fixation. Here, we report the discovery of two new lipoglycopeptides, desmamides A ( 1 ) and B ( 2 ), together with their aglycone desmamide C ( 3 ), from the nostocalean cyanobacterium Desmonostoc muscorum LEGE 12446 isolated from a cycad ( Cycas revoluta ) coralloid root. The chemical structures of the compounds were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The desmamides are decapeptides featuring O -glycosylation of tyrosine (in 1 and 2 ) and an unusual 3,5-dihydroxy-2-methyldecanoic acid residue. The biosynthesis of the desmamides was studied by substrate incubation experiments and bioinformatics. We describe herein the dsm biosynthetic gene cluster and propose it to be associated with desmamide production. The discovery of this class of very abundant (>1.5% d.w.) bacterial lipoglycopeptides paves the way for exploration of their potential role in root endosymbiosis.

Highlights of biosynthetic enzymes and natural products from symbiotic cyanobacteria

“…[43][44][45][46][47] Also isolated from the roots of a cycad is the cyanobacterium Desmonostoc muscorum LEGE 12446, found to produce the lipoglycopeptide desmamides (6)(7)(8). 48 Some natural product structural families long known to be produced by freeliving cyanobacteria, have also been identied within symbiotic systems (oen inferred by mass spectrometry fragmentation), Paul Michael D'Agostino received his PhD in 2014 from Western Sydney University under the supervision of Dr Michelle Mof-tt. Aer his PhD, he worked in the laboratory of Prof. Brett Neilan at the University of New South Wales.…”

“…43–47 Also isolated from the roots of a cycad is the cyanobacterium Desmonostoc muscorum LEGE 12446, found to produce the lipoglycopeptide desmamides ( 6–8 ). 48 Some natural product structural families long known to be produced by free-living cyanobacteria, have also been identified within symbiotic systems (often inferred by mass spectrometry fragmentation), including the UV sunscreen mycosporine-like amino acids and scytonemin; 35 anabaenopeptins, nostocyclopeptides, nostopeptolin, 46,49 as well as the hepatotoxic microcystins and nodularin. 50–52 Whilst these structural families have been well described previously, there appears to be structural discrepancies between cyanobionts and free-living cyanobacteria, with symbiotic environments likely to provide novel analogues of these scaffold families.…”

Staphylococcus aureus is able to generate resistance to novel lipoglycopeptide antibiotic gausemycin A

“…Natural lipoglycopeptides are rare and are grouped in a small number of structural classes including gausemycins (Freitas et al, 2022 ). The present work is the only second evidence of bacterial resistance to lipoglycopeptides after Schmidt's study of ramoplanin-resistant S. aureus (Schmidt et al, 2010 ).…”

Primary Structure of Glycans by NMR Spectroscopy

“…Furthermore, the peptide sequential information can readily be obtained in D 2 O solution from a 1 H, 13 C-BS-CT-HMBC spectrum recorded with a selective excitation pulse centered at the carbonyl carbon resonances, which provides a correlation map in which each carbonyl resonance of the peptide bonds is correlated via 2 J CH and 3 J CH coupling constants to intra- and inter-residual protons, respectively (Figure c−e) . This strategy was recently implemented in DMSO- d 6 solution for sequence assignment of cyclic lipoglycopeptides isolated from the cyanobacterium D. muscorum …”