Cyclic Hexapeptides from the Deep South China Sea-Derived Streptomyces scopuliridis SCSIO ZJ46 Active Against Pathogenic Gram-Positive Bacteria

Abstract

Three new cyclohexapeptides, desotamides B-D (2-4), and the known desotamide (1) were isolated from marine microbe Streptomyces scopuliridis SCSIO ZJ46. The sequences and absolute configurations of 2-4 were elucidated on the basis of high-resolution spectroscopic data, Marfey's method, and chiral-phase HPLC data. Desotamide C (3) contains a unique N-formyl-kynurenine residue, whereas 4 lacks formylation at the same site. Compounds 1 and 2 displayed notable antibacterial activities against strains of Streptococcus pnuemoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis (MRSE), and structure activity relationship studies revealed the indispensability of the Trp component for antibacterial activity within this new scaffold.

Solid-phase synthesis of cyclic hexapeptides wollamides A, B and desotamide B

“…Again, following purification with the base-modified silica gel column chromatography, the 1 H NMR spectrum of synthetic desotamide B ( 1 ) was also in agreement with that of the isolated natural product. 1,3 However, in the case of wollamide A ( 3 ), column purification with amine functionalized silica gel resulted in a product (Fig. 2C) that had notable 1 H NMR differences (e.g., in the regions of 4–4.75 ppm and 8.25–8.5 ppm) from isolated natural product.…”

“…1), a cyclic hexapeptide, was first described in 2014 by Ju and colleagues as a secondary metabolite from a deep-sea Streptomyces scopuliridis (SCSIO ZJ46). 1 To date, this rare family of cyclic peptides also includes desotamides A, 2 B-D, 1 E-F, 3 and G. 4 In the same year, 1 was also reported by Capon and colleagues as a metabolite from a soil Streptomyces nov. sp. (MST-115088) along with two new cyclic hexapeptides, wollamides A ( 3 ) and B ( 2 ) (Fig.…”

“…1,3 Desotamide B has been reported to have moderate Gram-positive antibacterial activity against S. aureus, S. pneumoniae , 1 and B. subtilis . 3 Notably, the basic d -Orn in wollamides A and B expanded the antibacterial spectrum to include mycobacteria (IC 50 s = 2.8 and 3.1 mM against M. bovis , respectively) that was not exhibited by desotamides A, B, E or F. 3 In addition to the M. bovis activity reported for these d -Orn homologues, wollamides also displayed higher IC 50 values (>30 μM) against mammalian cancer cell lines (SW620 and NCIH-460), indicating potential antibacterial and/or antimycobacterial selectivity.…”

Deep Sea Actinomycetes and Their Secondary Metabolites

“…Three glycosyltransferases (GTs) LobG1-LobG3 genes-inactivation mutants yielded five different glycosylated metabolites, and the result suggested that LobG3 as an iterative GT to attach two L-digitoxoses (Li et al, 2013). Desotamides B, C and D together with a known desotamide A were obtained from deep sea derived Streptomyces scopuliridis SCSIO ZJ46, recovered from sediment sample collected at a depth of 3,536 m in the South China Sea (Song et al, 2014). A 39 kb gene cluster governing the biosynthesis of the anti-infective desotamides has been isolated from the strain.…”

Marine biodiversity: exploring bioactive chemical space

“…For example, while the regiochemistry of L and D-Ala residues in the cyclohexadepsipeptide paecilodepsipeptide A (7.01) were inferred (unconvincingly) from NOESY correlations, 216 the regiochemistry of L and D-Asn in mojavensin A (7.02), 217 and L and D-Leu in the cyclohexapeptide desotamides B-D (7.03-7.05) 218 and desotamide G (7.06) 219 were asserted without comment, and the regiochemistry of L and D-Leu residues in the lipopeptide hallobacillin (7.07) was left unassigned. 220 As evidence of the effort required to secure unambiguous assignments, the regiochemistry of L and D-Leu in the cyclohexapeptide desotamide A (7.08) relied on the total synthesis of multiple isomers, 221 while the regiochemistry of L and D-Ile in the cyclooctapeptide surugamides A-E (7.09-7.13) relied on partial hydrolysis to tri and dipeptide fragments, which were in turn identified by a combination of Marfey's analyses and HPLC comparison to six synthetic dipeptides.…”