Kijanimicin. 2. Structure and absolute stereochemistry of kijanimicin

Mallams, Alan K.; Puar, Mohindar S.; Rossman, Randall; McPhail, Andrew T.; Macfarlane, R. D.

doi:10.1021/ja00403a063

Cited by 68 publications

(29 citation statements)

References 3 publications

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“…The high-resolution mass of this compound was 1,209.5958 (m/z [MϩNa] ϩ ), and its molecular formula was C 61 H 90 N 2 O 21 (Fig. 3), which corresponds precisely to that reported for kijanimicin 53 (34). A further analysis of the carbon NMR spectrum for this compound in FIG.…”

Section: Distribution Of Biosynthetic Genessupporting

confidence: 72%

“…1) and distinct loci (14), of which five shared Ն85% amino acid identity with top BLAST hits from experimentally characterized biosynthetic pathways (Table 2). Of these five sequences, three had top BLAST matches to genes associated with the biosynthesis of the polyketide-derived macrolide kijanimicin (34). Two additional KS sequences formed a separate cluster and had high levels of sequence identity with KSs associated with the biosynthesis of the polyketide tautomycin (30).…”

Section: Distribution Of Biosynthetic Genesmentioning

confidence: 99%

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Sequence-Based Analysis of Secondary-Metabolite Biosynthesis in Marine Actinobacteria

Gontang

Gaudêncio

Fenical

et al. 2010

Appl Environ Microbiol

110

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A diverse collection of 60 marine-sediment-derived Actinobacteria representing 52 operational taxonomic units was screened by PCR for genes associated with secondary-metabolite biosynthesis. Three primer sets were employed to specifically target adenylation domains associated with nonribosomal peptide synthetases (NRPSs) and ketosynthase (KS) domains associated with type I modular, iterative, hybrid, and enediyne polyketide synthases (PKSs). In total, two-thirds of the strains yielded a sequence-verified PCR product for at least one of these biosynthetic types. Genes associated with enediyne biosynthesis were detected in only two genera, while 88% of the ketosynthase sequences shared greatest homology with modular PKSs. Positive strains included representatives of families not traditionally associated with secondary-metabolite production, including the Corynebacteriaceae, Gordoniaceae, Intrasporangiaceae, and Micrococcaceae. In four of five cases where phylogenetic analyses of KS sequences revealed close evolutionary relationships to genes associated with experimentally characterized biosynthetic pathways, secondary-metabolite production was accurately predicted. Sequence clustering patterns were used to provide an estimate of PKS pathway diversity and to assess the biosynthetic richness of individual strains. The detection of highly similar KS sequences in distantly related strains provided evidence of horizontal gene transfer, while control experiments designed to amplify KS sequences from Salinispora arenicola strain CNS-205, for which a genome sequence is available, led to the detection of 70% of the targeted PKS pathways. The results provide a bioinformatic assessment of secondarymetabolite biosynthetic potential that can be applied in the absence of fully assembled pathways or genome sequences. The rapid identification of strains that possess the greatest potential to produce new secondary metabolites along with those that produce known compounds can be used to improve the process of naturalproduct discovery by providing a method to prioritize strains for fermentation studies and chemical analysis.Microbial natural products represent the primary resource from which new medicines are derived, accounting for approximately half of the antibiotics discovered as of 2002 (6). Over the past several decades, however, drug discovery efforts have moved away from microbial products (29), in part due to a reduction in the ratio of new chemical entities discovered relative to the isolation of known metabolites (3) and the challenges associated with developing effective "dereplication" methods to improve the efficiency of the discovery process. More recently, the rise in drug-resistant pathogens has left many current antibiotics obsolete, while the limited success of alternative discovery strategies, such as combinatorial chemistry, have created a void in the pipeline of new drug leads (39). The response to this need includes renewed interest in a group of actinobacteria commonly called actinomycetes (defined here as ba...

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Section: Distribution Of Biosynthetic Genessupporting

confidence: 72%

Section: Distribution Of Biosynthetic Genesmentioning

confidence: 99%

Sequence-Based Analysis of Secondary-Metabolite Biosynthesis in Marine Actinobacteria

Gontang

Gaudêncio

Fenical

et al. 2010

Appl Environ Microbiol

110

View full text Add to dashboard Cite

show abstract

“…12 The deduced absolute configuration was identical with that known for this antibiotic family. 13,14 Spirotetronates represented by kijanimicin 15 feature a trans-D 1 -octalin unit and a tetronic acid moiety spiro-linked with a cyclohexene ring. To date, over 50 related metabolites have been discovered from actinomycetes.…”

Section: Resultsmentioning

confidence: 99%

Nomimicin, a new spirotetronate-class polyketide from an actinomycete of the genus Actinomadura

et al. 2012

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Nomimicin (1), a new spirotetronate-class polyketide, was isolated from the culture broth of an actinomycete of the genus Actinomadura. Its structure was established by spectroscopic methods, and the absolute configuration was determined by a combination of NOESY experiment, J-based configuration analysis and the modified Mosher method. Nomimicin (1) showed antimicrobial activity against Micrococcus luteus, Candida albincans and Kluyveromyces fragilis. Keywords: Actinomadura; polyketide; spirotetronate INTRODUCTION Microbial secondary metabolites have been the most productive source of small molecules for the development of drugs. 1 Almost a half of the known microbial bioactive compounds are derived from actinomycetes, and specifically Streptomyces accounts for more than 70% of the actinomycete-derived metabolites. 2 Among the nonStreptomyces species, Micromonospora is the leading producer of secondary metabolites, including polyketides, peptides and glycosides, whereas Actinomadura is known as a producer of chemically and biologically unique polyketides such as antitumor enediynes, 3 mannose-binding quinone glycosides with antifungal and anti-HIV activities 4 and anticoccidial polyethers, 5 accounting for up to 350 compounds reported as of 2005. 2 During our continuing investigation on the metabolites from actinomycetes of nonStreptomyces group, 6,7 a new spirotetronate antibiotic of polyketide origin, nomimicin (1, Figure 1), was isolated from the culture extract of Actinomadura sp. TP-A0878. In this paper, we describe the isolation, structural determination and biological properties of 1.

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“…The spirotetronate antibiotics comprise of a class of antibacterial and antitumor natural products, such as antlermicin, 13 chlorothricin, 14 kijanimicin, 15 decatromicins, 16 saccharocarcins, 17 tetrocarcins 18 and versipelostatins. 19 A pair of spirotetranate antibiotics lobophorins A (3) and B (4), previously isolated from an alga-associated acintobacterium, were shown to exhibit anti-inflammatory but no antimicrobial activities.…”

Section: Biological Activitymentioning

confidence: 99%

Lobophorins E and F, new spirotetronate antibiotics from a South China Sea-derived Streptomyces sp. SCSIO 01127

Niu

Chen

et al. 2011

J Antibiot

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The strain SCSIO 01127, isolated from the South China Sea sediment, was identified as a member of Streptomyces by the 16S rDNA sequence analysis. Two new spirotetronate antibiotics lobophorins E (1) and F (2), along with two known analogs lobophorins A (3) and B (4), were isolated from Streptomyces sp. SCSIO 01127. Their structures were elucidated on the basis of detailed IR, NMR and MS spectroscopic analyses. The new compound lobophorin F (2) showed antibacterial activities against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 with MIC values of 8 mg ml À1 for both the strains, better than that of lobophorin B (4). Lobophorin F (2) also displayed better cytotoxic activities than lobophorin B (4), with IC 50 of 6.82, 2.93 and 3.16 mM against SF-268, MCF-7 and NCI-H460, respectively.

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Kijanimicin. 2. Structure and absolute stereochemistry of kijanimicin

Cited by 68 publications

References 3 publications

Sequence-Based Analysis of Secondary-Metabolite Biosynthesis in Marine Actinobacteria

Sequence-Based Analysis of Secondary-Metabolite Biosynthesis in Marine Actinobacteria

Nomimicin, a new spirotetronate-class polyketide from an actinomycete of the genus Actinomadura

Lobophorins E and F, new spirotetronate antibiotics from a South China Sea-derived Streptomyces sp. SCSIO 01127

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