Gausemycins A,B – Cyclic Lipoglycopeptides from Streptomyces Sp.

Abstract

We report a novel family of natural lipoglycopeptides produced by <i>Streptomyces</i> sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The com-pounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual posi-tions of D-amino acids, lack of the Ca<sup>2+</sup>-binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4-phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the or-nithine side chain. These major components of the peptide antibiotic family have pronounced activity against Gram-positive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. Gausemycins exhibit only slight Ca<sup>2+</sup>-dependence of an-timicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

Generation of Gausemycin A-resistant Staphylococcus aureus

“…We have taken daptomycin and ramoplanin to compare the features of the gausemycin A resistance formation against two antibiotics which having certain similarities with gausemycin A. Earlier, we showed that gausemycin А has a mode of action similar to that of membrane-active lipopeptide daptomycin [19], while structurally more resemble lipoglycopeptide ramoplanin [18].…”

“…Recently the new lipoglycopeptides were revealed among metabolites of actinomycete Streptomyces roseoflavus INA-Ac-5812. These lipoglycopeptides were first described in 2016 [17] and then were named as gausemycins A and B [18].…”

“…Gausemycin A is cyclic lipoglycopeptide, resembling anionic lipopeptides, but with a completely distinct peptide sequence. The closest structurally related compounds are the depsipeptides (daptomycin, taromycins, and cadazides) and the cyclopeptides (amphomycin, rumycins, and malacidins) [18].…”

Structure and biosynthesis of desmamides A-C, lipoglycopeptides from the endophytic cyanobacterium Desmonostoc muscorum LEGE 12446

“…Nevertheless and remarkably, O-glycosylation of Tyr is observed in several of these, namely in mannopeptimycins γ/d/ε 22 and in the gausemycins. 18 This decoration is also present in the fungal glycopeptide cycloaspeptide F 35 and in cacaoidin, 36 a recently described ribosomallysynthesized and post-translationally modified (RiPP) glycopeptide.…”

“…This designation has been used to encompass both glycosylated lipopeptides and acylated glycopeptides. 17,18 Natural lipoglycopeptides are rare and are grouped in a small number of structural classes: the cyanobacterial hassallidins/balticidins, 19,20 the actinobacterial teicoplanin/teichomycins, 21 mannopeptimycins (γ, d and ε), 22 ramoplanins 23 and gausemycins, 18 as well as occidiofungins produced by a Gram-negative Burkholderia strain. 24 Potent antibacterial or antifungal activities are associated with each of these compound classes; teicoplanin and related semisynthetic lipoglycopeptides are used in the clinic to treat serious infections caused by Gram-positive bacteria.…”