Sugar Phosphate Cyclases (SPCs) catalyze the cyclization of sugar phosphates to produce a variety of cyclitol intermediates that serve as the building blocks of many primary metabolites, e.g., aromatic amino acids, and clinically relevant secondary metabolites, e.g., aminocyclitol/ aminoglycoside and ansamycin antibiotics. Feeding experiments with isotopically-labeled cyclitols revealed that cetoniacytone A, a unique C 7 N-aminocyclitol antibiotic isolated from an insect endophytic Actinomyces sp., is derived from 2-epi-5-epi-valiolone, a product of SPC. Using heterologous probes from the 2-epi-5-epi-valiolone synthase class of SPCs, an SPC homolog gene, cetA, was isolated from the cetoniacytone producer. CetA is closely related to BE-orf9 found in the BE-40644 biosynthetic gene cluster from Actinoplanes sp. strain A40644. Recombinant expression of cetA and BE-orf9 and biochemical characterization of the gene products confirmed their function as 2-epi-5-epi-valiolone synthases. Further phylogenetic analysis of SPC sequences revealed a new clade of SPCs that may regulate the biosynthesis of a novel set of secondary metabolites.

Three new fungal polyketide metabolites, chaetocyclinone A to C, were produced by cultures of Chaetomium sp. (strain Gö 100/2), which was isolated from marine algae. The structures of the novel compounds were established by detailed spectroscopic analysis. Additionally, an X‐ray analysis of chaetocyclinone C (5) was performed. Chaetocyclinone A (1) exhibits inhibitory activity against selected phytopathogenic fungi. The biosynthesis of 1 and 5 was studied by feeding 13C‐labelled acetate. The results suggest the polyketide pathway for the isolated metabolites. In the case of chaetocyclinone C (5), we assume an unusual condensation of two highly reactive heptaketide intermediates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The antibacterial orsellides A–E (1–5), novel esters consisting of orsellinic acid (6) and a 6‐deoxyhexose, were isolated from Chaetomium sp. (strain Gö 100/9) together with the known metabolites globosumones A (7) and B (8). The structures of the new compounds were elucidated by detailed spectroscopic analysis. The biosynthesis of these metabolites was studied by feeding 13C‐labelled precursors to growing cultures of strain Gö 100/9. The sugar moieties of the orsellides A–E (1–5) as well as the side chains of globosumones A (7) and B (8) originate from carbohydrate intermediates. Thus, the orsellides are rare examples for fungal metabolites containing deoxyhexose building blocks that are normally characteristic for bacterial secondary metabolites. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Cetoniacytone A (1) and some related minor components (2, 6, 7) were produced by Actinomyces sp. (strain Lu 9419), which was isolated from the intestines of a rose chafer (Cetonia aureata). The structures of the novel metabolites were established by detailed spectroscopic analysis. The absolute configuration of 1 was determined by X-ray analysis and derivatisation with chiral acids. 1 exhibits a significant cytotoxicity against selected tumor cell lines. The biosynthesis of 1 was studied by feeding 13C labelled precursors. The results suggest that the characteristic p-C7N skeleton of the aminocarba sugar is formed via the pentose phosphate pathway by cyclisation of a heptulose phosphate intermediate.In the course of our screening program for new secondary metabolites2) we investigated endosymbionts, which were isolated from several members of Crustacea (wood-lice), Myriapoda (millipedes) and Hexapoda (insects)3). In the culture broth of Actinomyces sp. (strain Lu 9419), which was isolated from the intestines of a rose chafer (Cetonia aureata) we identified two novel aminocarba sugars, which were named cetoniacytone A (1) and B (2). Carba sugars and aminocarba sugars are widespread metabolites produced especially by actinomycetes. Many of their natural derivatives are biologically active, well known examples are validamycin A4) and acarbose5), both containing valienamine (3). Structurally related to the cetoniacytones are epoxyquinomicin C (4) and D (5), which were isolated from the culture broth of an Amycolatopsis sp6), They possess anti-arthritic effects on type II collagen-induced arthritis in mice7) and inhibited the histidine decarboxylase in rat embryos8).Different biosynthetic pathways leading to carbocyclic Additionally we report the structures of three novel minor components, cetoniacytone B (2) and two aromatic analogues (6, 7). Fermentation and IsolationActinomyces sp. (strain Lu 9419) was cultivated in shaking flasks, using oatmeal medium with sodium acetate described metabolites were only found in the culture filtrate, which was separated from the mycelium by centrifugation. The filtrate was passed through Amberlite(R) XAD-2, from which the metabolites were eluated with methanol. The evaporation residue was separated by successive column chromatography on silica gel and Sephadex LH-20 leading to 10-15mg/liter of cetoniacytone A (1). Besides 4.8mg/liter of 1a cultivation in absence of sodium acetate yielded 5.6mg/liter of cetoniacytone B (2). Addition of glucose (1g/liter) after 48 hours, when the production of 1 has just started, increased the yield of 1 to 20.25mg/liter. However, addition of glucose at the beginning of the fermentation had no influence on the yield of 1. A scale-up using a 50-liter stirring fermenter yielded 85mg of 1 and allowed the isolation of minor components: 34mg of 2, 5-dihydroxy-4-hydroxymethylacetanilide (6), 4.1mg of 2, 5-dihydroxy-4-methoxymethylacetanilide (7) and 9.4mg of 2-acetamido-phenol. All compounds are detectable on silica gel TLC-plates with UV light at 254nm ...

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