Apratoxin D, a potent cytotoxic cyclodepsipeptide from papua new guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida

Cancer cell toxicity-guided fractionation of extracts of the Papua New Guinea marine cyanobacteria Lyngbya majuscula and Lyngbya sordida led to the isolation of apratoxin D (1). Compound 1 contains the same macrocycle as apratoxins A and C but possesses the novel 3,7-dihydroxy-2,5,8,10,10-pentamethylundecanoic acid as the polyketide moiety. The planar structures and stereostructures of compound 1 were determined by extensive 1D and 2D NMR and MS data analyses and by comparison with the spectroscopic data of apratoxins A and C. Apratoxin D (1) showed potent in vitro cytotoxicity against H-460 human lung cancer cells with an IC 50 value of 2.6 nM.     

Naphthoquinone-like polyketide isolated from Streptomyces sp. RI-77 and its predicted biosynthetic pathway

A novel naphthoquinone-like polyketide, JBIR-85 (1), with a unique skeleton and antioxidative activity was isolated from a culture of Streptomyces sp. RI-77. The planar structure of 1 was established on the basis of extensive NMR and MS analyses. The structure of 1 including the absolute configuration was established via X-ray crystallographic analysis. Since 1 exhibits a unique skeleton, we performed feeding experiments to reconfirm the structure and predict the biosynthetic pathway.     

Maklamicin, an antibacterial polyketide from an endophytic Micromonospora sp

A new spirotetronate-class polyketide, maklamicin (1), was isolated from the culture extract of an endophytic actinomycete of the genus Micromonospora. The structure and relative configuration of 1 were elucidated by interpretation of NMR and other spectroscopic data, and the absolute configuration was determined using the modified Mosher method. Maklamicin (1) showed strong to modest antimicrobial activity against Gram-positive bacteria.     

Phaeochromycins A-E, anti-inflammatory polyketides isolated from the soil actinomycete Streptomyces phaeochromogenes LL-P018

Five new polyketide metabolites, phaeochromycins A-E (1-5), were isolated from an actinomycete designated Streptomyces phaeochromogenes LL-P018, cultured from a soil sample collected from a riverbank in Westevenger, Germany. Phaeochromycins A and C were found to be weak inhibitors of MAPKAP kinase-2 (IC50 = 39 and 130 microM, respectively). The structures of the compounds were determined by spectroscopic analysis, primarily two-dimensional NMR, and revealed that phaeochromycins A, B, C, and E were octaketides, elaborated from a C4 starter unit, related to shunt products of the actinorhodin pathway, namely, mutactin, dehydromutactin, SEK34b, and BSM1. Phaeochromycin D (4) is an unusual partially cyclized degraded octaketide intermediate.     

Pinpointing pseurotins from a marine-derived Aspergillus as tools for chemical genetics using a synthetic lethality yeast screen

A new compound of mixed polyketide synthase-nonribosomal peptide synthetase (PKS/NRPS) origin, 11- O-methylpseurotin A ( 1), was identified from a marine-derived Aspergillus fumigatus. Bioassay-guided fractionation using a yeast halo assay with wild-type and cell cycle-related mutant strains of Saccharomyces cerevisiae resulted in the isolation of 1, which selectively inhibited a Hof1 deletion strain. Techniques including 1D and 2D NMR, HRESIMS, optical rotation, J-based analysis, and biosynthetic parallels were used in the elucidation of the planar structure and absolute configuration of 1. A related known compound, pseurotin A ( 2), was also isolated and found to be inactive in the yeast screen.     

Phaeofurans and sorbicillin analogues from a fungicolous Phaeoacremonium species (NRRL 32148)

Two new benzofuran-derived metabolites of polyketide origin called phaeofurans A and B (1 and 2), along with three sorbicillin analogues (3-5), have been obtained from a fungicolous isolate of the genus Phaeoacremonium (NRRL 32148). The structures were determined by analysis of MS and 2D NMR data. The antifungal effects of the extract were ascribed to the sorbicillin analogues.     

Caryophyllene sesquiterpenoids from a fungicolous isolate of Pestalotiopsis disseminata

Three new caryophyllene-type sesquiterpene alcohols, 6-hydroxypunctaporonin E (1), 6-hydroxypunctaporonin B (2), and 6-hydroxypunctaporonin A (3), have been isolated from cultures of the fungicolous fungus Pestalotiopsis disseminata. The structures of 1-3 were determined mainly by analysis of 1D and 2D NMR data. The structure and absolute configuration of 6-hydroxypunctaporonin E (1) was confirmed through X-ray crystallographic analysis of its mono-bromobenzoate derivative. Compounds 1 and 2 showed activity against Gram-positive bacteria.     

Myxochromide B3, a new member of the myxochromide family of secondary metabolites

Myxochromides are cyclic depsipeptides with an unsaturated polyketide side chain, which have been reported from different myxobacterial species, e.g., Myxococcus xanthus and Stigmatella aurantiaca. To date, myxochromides are subdivided into the groups A and S, according to their peptidic core structure. The peptide moiety of the new myxochromide B3 (1), which was isolated from a myxobacterial strain of the genus Myxococcus, differs from that of myxochromides A and S. Compound 1 thus is the first representative of a new group of myxochromides. For myxochromide A3 (2) the complete and assigned spectroscopic data are described. For the structure elucidation one- and two-dimensional NMR spectroscopy as well as mass spectrometry have been applied. Configurational analysis has been accomplished by chiral GC-MS and HPLC.     

Abyssomicin I, a modified polycyclic polyketide from Streptomyces sp. CHI39

Abyssomicin I (1), a new modified polycyclic polyketide, was isolated from the culture extract of a soil-derived Streptomyces sp. The structure of 1 was elucidated by interpretation of NMR and other spectroscopic data. The stereochemistry of the new compound was assigned by NOE analysis, chemical derivatization, and application of the modified Mosher method. While 1 was inactive against bacteria and yeasts, the oxidized derivative 7 showed weak activities against gram-positive bacteria. Compounds 1 and 7 exhibited inhibitory effects on tumor cell invasion with IC(50) values of 11 and 0.21 μM, respectively.     

Salinipyrones and pacificanones, mixed-precursor polyketides from the marine actinomycete Salinispora pacifica

Chemical examination of a phylogenetically unique strain of the obligate marine actinomycete Salinispora pacifica led to the discovery of four new polyketides, salinipyrones A and B ( 1, 2) and pacificanones A and B ( 3, 4). These compounds appear to be derived from a mixed-precursor polyketide biosynthesis involving acetate, propionate, and butyrate building blocks. Spectral analysis, employing NMR, IR, UV, and CD methods and chemical derivatization, was used to assign the structures and absolute configurations of these new metabolites. Salinipyrones A and B displayed exactly opposite CD spectra, indicating their pseudoenantiomeric relationship. This relationship was shown to be a consequence of the geometric isomerization of one double bond. The phenomenon of polyketide module skipping is proposed to explain the unusual biosynthesis of the salinipyrones and the pacificanones.     

Totopotensamides, polyketide-cyclic peptide hybrids from a mollusk-associated bacterium Streptomyces sp

Two new compounds, the peptide-polyketide glycoside totopotensamide A (1) and its aglycone totopotensamide B (2), were isolated from a Streptomyces sp. cultivated from the gastropod mollusk Lienardia totopotens collected in the Philippines. The compounds contain a previously undescribed polyketide component, a novel 2,3-diaminobutyric acid-containing macrolactam, and a new amino acid, 4-chloro-5,7-dihydroxy-6-methylphenylglycine. The application of Marfey's method to phenylglycine derivatives was explored using quantum mechanical calculations and NMR.     

Diverse metabolic profiles of a Streptomyces strain isolated from a hyper-arid environment

The metabolic profile of Streptomyces sp. strain C34, isolated from the Chilean hyper-arid Atacama Desert soil, is dependent on the culture media used for its growth. The application of an OSMAC approach on this strain using a range of cultivation media resulted in the isolation and identification of three new compounds from the rare class of 22-membered macrolactone polyketides, named chaxalactins A-C (1-3). In addition, the known compounds deferroxamine E (4), hygromycin A (5), and 5″-dihydrohygromycin A (6) were detected. The isolated compounds were characterized by NMR spectroscopy and accurate mass spectrometric analysis. Compounds 1-3 displayed strong activity against Gram-positive but weak activity Gram-negative strains tested.     

New antiviral cassane furanoditerpenes from Caesalpinia minax.

A bioassay-guided study led to the isolation of five new cassane furanoditerpenes, designated as caesalmin C (1), D (2), E (3), F (4), and G (5), along with stigmasterol (6) from the seeds of Caesalpinia minax. The (1)H and (13)C NMR spectra were completely assigned by using a combination of 2D NMR analyses. The structures of all five furanoditerpenes were confirmed by X-ray analyses. The structure of 6 was verified by X-ray analysis for the first time. The bioassay results showed that the anti-Para3 virus activity of tetracyclic furanoditerpenoids 1-4 is more potent than that of the furanoditerpenoid lactone 5, which is in turn better than 6. As the major components of the plant possess significant potent activity, it may be feasible to develop new antiviral agents from this source.     

Daryamides A-C, weakly cytotoxic polyketides from a marine-derived actinomycete of the genus Streptomyces strain CNQ-085

In the course of our continuing search for new antitumor-antibiotics from marine-derived actinomycete bacteria, four new cytotoxic compounds, designated as daryamides A (1), B (2), and C (3) and (2E,4E)-7-methylocta-2,4-dienoic acid amide (4), were isolated from the culture broth of a marine-derived Streptomyces strain CNQ-085. The structures of these new compounds were assigned by detailed interpretation of spectroscopic data. The relative configuration of 1 was determined by comprehensive NMR analysis, while the absolute configuration of 1 was determined as 4S,5R using the modified Mosher method. The daryamides show weak to moderate cytotoxic activity against the human colon carcinoma cell line HCT-116 and very weak antifungal activities against Candida albicans.     

Langkolide, a 32-membered macrolactone antibiotic produced by Streptomyces sp. Acta 3062

A new 32-membered macrolactone antibiotic, named langkolide, was isolated from the mycelium of Streptomyces sp. Acta 3062. The langkolide structure was determined by HR-MS and 1D and 2D NMR as a 32-membered macrolactone connected from an overhanging polyketide tail to a naphthoquinone unit mediated by two carbohydrate moieties. The producing strain was isolated from a rhizosphere soil of Clitorea sp. collected at Burau Bay, Langkawi, Malaysia, and was characterized by its morphological and chemotaxonomic features in addition to its 16S rRNA gene sequence. It was identified as a member of the Streptomyces galbus clade. Langkolide exhibited various bioactivities including antimicrobial and antiproliferative activities. Furthermore, langkolide inhibited human recombinant phosphodiesterase 4 with an IC(50) value of 0.48 μM.     

Lowdenic acid: a new antifungal polyketide-derived metabolite from a new fungicolous Verticillium sp

Lowdenic acid (1), a new antifungal metabolite with an unusual structure and a mixed biogenetic origin, has been obtained from nonsporulating cultures of a previously undescribed Verticillium sp. (MYC-406 = NRRL 29280) that was isolated as a colonist of polypore basidiomata. The gross structure of 1 was proposed by analysis of NMR data and confirmed by X-ray diffraction analysis, which enabled assignment of relative stereochemistry. Compound 1 occurs as an equilibrium E/Z mixture. The known antifungal metabolite canescin A (2) was also isolated.     

Chemical constituents of a marine fungus, Arthrinium sacchari

Three new diterpenes, myrocin D (1), libertellenone E (2), and libertellenone F (3), and a new isocoumarin, decarboxyhydroxycitrinone (4), were isolated from the marine fungus Arthrinium sacchari, together with three known compounds (5-7). The structures of 1-4 were elucidated from spectroscopic data (NMR, MS, IR), and the absolute configurations of 1-3 were determined by X-ray diffraction analysis. The antiangiogenic activity of these compounds was evaluated by measuring their antiproliferation effects on human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs). Compounds 4-7 showed inhibitory activity.     

Discovery, synthesis, and insecticidal activity of cycloaspeptide E

Several Penicillia and one Tricothecium strain produced a new, insecticidally active member of the cycloaspeptide family, with the proposed name cycloaspeptide E (1). The structure, which was determined on the basis of spectroscopic (NMR, UV, MS) data and Marfey amino acid analysis, was the tyrosine desoxy version of cycloaspeptide A (2). Two synthetic routes to compound 1 were developed: one a partial synthesis from 2 and the other a total synthesis from methyl alaninate hydrochloride. Cycloaspeptide E, the first member of this series not to contain a tyrosine moiety, is also the first to be reported with insecticidal activity.     

A new cytotoxic calyculinamide derivative,geometricin A,from the Australian sponge Luffariella geometrica

Geometricin A (1), together with the known compounds (7E,12E,18S,20Z)-variabilin (2), clathryimine A (3), tryptophol (4), and L-tryptophan, has been isolated from the methanol extract of the Australian sponge Luffariella geometrica. The structure of the new compound geometricin A (1) was elucidated by employing spectroscopic techniques (NMR, MS, UV, and IR) and by comparison of its NMR data with those of the calyculins and calyculinamides. Geometricin A (1) was found to be moderately cytotoxic toward the tumor cell lines HM02 and HEPG2 with GI50's of 1.7 and 2.8 microg/mL, respectively, and to have antialgal activity (growth inhibition zone 5 mm at the 50 microg level).     

Isolation and characterization of new epothilone analogues from recombinant Myxococcus xanthus fermentations

Nine new epothilone analogues (6-8, 10, 11a, 11b, 12, 13, and 15) were isolated from fermentations of Myxococcus xanthus strains engineered with modified polyketide synthase genes. The epothilone structures were elucidated primarily through interpretation of 1D and 2D NMR data. 4-Desmethyl-10,11-didehydroepothilone D (6) displayed activity against several tumor cell lines, including a multi-drug-resistant cell line.