Catechoserine, a new catecholate-type inhibitor of tumor cell invasion from Streptomyces sp.

Abstract

Microbial natural products represent the primary resource for drug discovery, accounting for 420 000 bioactive compounds discovered to date. 1 The majority of microbial drug discovery research has focused on actinomycetes, in particular strains of the chemically prolific genus Streptomyces. Drug discovery efforts from actinomycetes, however, have been in decline, in part because of the relatively high frequency of the isolation of known compounds. To overcome this problem, extensive attempts have been directed toward the development of effective strain selection methods to improve the efficiency of the discovery process. 2-4 Sequence-based strain selection is one of the approaches to eliminate the strains which might be studied previously. Although it is not clear whether the phylogenic novelty is associated with the production ability of new compounds, recent studies have shown the occurrence of new metabolites in Streptomyces species that have a low 16S rRNA gene sequence homology to the known species. [5][6][7] In our continuing investigation on chemical diversity within this group, 8-10 a Streptomyces strain that shared a low 16S rRNA gene identity (96.3%) with the nearest type strain for S. albus was found to produce a new catecholate derivative, catechoserine (1), along with two known biosynthetically related metabolites, N,N¢-bis (Figure 1).The producing-strain TP-A0874 was isolated from a compost sample collected in Ishikawa, Japan, and identified as a member of the genus Streptomyces by 16S rRNA gene sequence analysis. The whole culture broth of strain TP-A0874 cultured in A-3M liquid medium was separated into the supernatant and the mycelium. The latter was then extracted with methanol, and the organic solvent was removed under reduced pressure. The remaining aqueous solution was combined with the supernatant and fractionated by HP-20 resin column chromatography. The fractions were further purified by reversed-phase HPLC to yield compounds 1-3.

A Metabolite Produced by Gut Microbes Represses Phage Infections in Vibrio cholerae

“…Subsequent 1D and 2D NMR spectroscopy analyses (Table S3, Figures S2–S6) confirmed that the active compound has an identical planar structure to that of linear enterobactin . Optical rotation measurement ([α] D 23 + 13, c 0.10, MeOH) confirmed that the absolute stereochemistry of LinEnt matched the published form, which is constructed from l -serine …”

“…Tandem mass spectrometry (MS/MS) analysis of this compound (Figure S1) revealed a fragmentation pattern that matches substructures of linear enterobactin (LinEnt, Figure c), a byproduct of enterobactin biosynthesis and utilization . Subsequent 1D and 2D NMR spectroscopy analyses (Table S3, Figures S2–S6) confirmed that the active compound has an identical planar structure to that of linear enterobactin . Optical rotation measurement ([α] D 23 + 13, c 0.10, MeOH) confirmed that the absolute stereochemistry of LinEnt matched the published form, which is constructed from l -serine …”

“…Because LinEnt is a siderophore produced by certain Streptomyces spp. and E. coli , , we hypothesized that it inhibits phage proliferation by sequestering iron away from V. cholerae . To test if the phage inhibition was the result of iron sequestration by LinEnt, we saturated LinEnt with iron and added this Fe-LinEnt complex to V. cholerae culture prior to phage infection.…”

Butenolides from Streptomyces albus J1074 Act as External Signals To Stimulate Avermectin Production in Streptomyces avermitilis

“…Mycelia were harvested after incubation of the flask on a reciprocal shaker (120 spm) at 28°C for 3 days. The seed (30) in a 500-ml baffled flask on a reciprocal shaker (120 spm) at 28°C, followed by incubation for 3 days. The culture broth was extracted twice with an equal volume of ethyl acetate.…”

Draft Genome Sequence of Streptomyces sp. TP-A0874, a Catechoserine Producer

“…TP-A0874, was isolated from a compost sample collected in Ishikawa, Japan, and found to produce a new catecholate derivative designated catechoserine, along with two known biosynthetically related metabolites, N , N ′-bis(2,3-dihydroxybenzoyl)- O - l -seryl- l -serine and N , N ′, N ′-tris(2,3-dihydroxybenzoyl)- O - l -seryl- O - l -seryl- l -serine. These three compounds share an N -2,3-dihydroxybenzoyl-L-serine as a common structural unit and inhibit the invasion of murine colon carcinoma 26-L5 cells ( 1 ). To identify the biosynthetic gene cluster for these compounds and assess the potential to produce other secondary metabolites, we sequenced the genome of Streptomyces sp.…”