Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

Abstract

A genome mining survey combined with metabolome analysis of publicly available strains identified Couchioplanes sp. RD010705, a strain belonging to an underexplored genus of rare actinomycetes, as a producer of new metabolites. HPLC-DAD-guided fractionation of its fermentation extracts resulted in the isolation of five new methyl-branched unsaturated fatty acids, (2E,4E)-2,4-dimethyl-2,4-octadienoic acid (1), (2E,4E)-2,4,7-trimethyl-2,4-octadienoic acid (2), (R)-(−)-phialomustin B (3), (2E,4E)-7-hydroxy-2,4-dimethyl-2,4-octadienoic acid (4), (2E,4E)-7-hydroxy-2,4,7-trimethyl-2,4-octadienoic acid (5), and one prenylated tryptophan derivative, 6-(3,3-dimethylallyl)-N-acetyl-ʟ-tryptophan (6). The enantiomer ratio of 4 was determined to be approximately S/R = 56:44 by a recursive application of Trost’s chiral anisotropy analysis and chiral HPLC analysis of its methyl ester. Compounds 1–5 were weakly inhibitory against Kocuria rhizophila at MIC 100 μg/mL and none were cytotoxic against P388 at the same concentration.

Krasilnikolides A and B and Detalosylkrasilnikolide A, Cytotoxic 20-Membered Macrolides from the Genus Krasilnikovia: Assignment of Anomeric Configuration by J-Based Configuration Analysis

“…Krasilnikolides A ( 1 ) and B ( 2 ) and detalosylkrasilnikolide A ( 3 ) are unique macrolides characterized by a ( Z )-2-(m)­ethyl-2-butenyl side chain. Glycosylation by 6dTal is unprecedented for macrolides, though modified 6dTal are seen in maduralide, callipeltosides, , or mandelalides. − Along with a series of results from our investigation on rare actinomycetes, the present work supports an idea that phylogenetically distant actinomycetes, even at the genus level, possess different secondary metabolite biosynthetic gene clusters, and hence unexplored or underexplored genera are promising as a source of unreported natural products. − The newly introduced diagnostic criteria of the JBCA method, used for the assignment of the α-glycosidic linkage of l -6dTal, complements the scope of this nonempirical and nondestructive stereochemical analysis. The updated JBCA method is especially useful when an aldohexopyranoside under study has a small anomeric 1 H– 1 H coupling constant.…”

Catellatolactams A–C, Plant Growth-Promoting Ansamacrolactams from a Rare Actinomycete of the Genus Catellatospora

“…To the best of our knowledge, eight metabolites are distantly related (Figure 8), which are Q-1047R from Pseudonocardia, 18 tetrapetalones A−D and ansaetherone produced by the same Streptomyces strain, 19,20 and cebulactams A1 and A2 from marine obligate Saccha-ropolyspora. 21 Thus, discovery of catellatolactams A−C (1−3), together with our previous studies, [6][7][8]22,23 demonstrates a strategic advantage of investigating underexplored rare actinomycetal genera as a source of unprecedented molecular architectures.…”

“…A large part of actinomycete metabolites, approximately over 70%, were found from Streptomyces , while no secondary metabolites are recorded from a substantial number of actinomycete genera . We recently reported several new bioactive compounds from such underexplored rare actinomycetes: short-chain unsaturated fatty acids from Couchioplanes ; a cyclic tripeptide and new oligomycin-class macrolides from Pseudosporangium ; and an N -acyl dehydrotryptophan from Actinomycetospora . − …”

Phytohabitols A–C, δ-Lactone-Terminated Polyketides from an Actinomycete of the Genus Phytohabitans

“…The C11 double bonds in 1 – 3 and lagunapyrones are one-carbon shifted from where anticipated by dehydration in polyketide chain elongation processes. Similar double-bond shiftings are found in the biosynthesis of several polyketides, but the precise enzymatic mechanism underlying this reaction has yet to be elucidated. − Discovery of new compounds from unexplored actinomycete genera warrants their higher biosynthetic potential in producing unreported secondary metabolites. − …”

“…To overcome this issue, several different approaches including exploration of untouched habitats such as marine and extreme environments, metagenomic approaches including heterologous expression of cryptic biosynthetic genes, and genome mining for efficient selection of potential candidate strains have been attempted to achieve improved outcomes. Our laboratory is currently focusing on rare actinomycete genera from which no or few natural products have been recorded. − …”