Nonaketides

These fluorescent compounds have now been isolated from Corti-narius cotoneus, C. melanotus, and C. venetus and characterised by spectroscopic and chemical methods as the nonaketide leprocybin (394) (Gabriel s pigment-B ), and its aglycone, leprocyboside (395) ( pigment-A ) (437), 

It is of interest that alongside predominant nonaketides several species belonging to Cortinarius, subgenus Leprocybe, also manufacture an octaketide derived anthraquinone in the form of dermolutein (305) (Table 26). 

The distribution of pigments among members of Cortinarius, subgenus Leprocybe, has been surveyed using thin layer chromatography and is of some importance to the systematic taxonomy of the group 264, 332, 333, 372, 406). 

Pigment Occurrence Colour M.p. TLC Ultraviolet/Vis. [ m.x(logE)] Infrared [Vco] 

Anhydro-leprolutein (398) Cortinarius cotoneus [5 x 10 %], C. psittacinus, C. subannulatus (590) Orange 320° 0.28 Violet — — 

Incorporations of singly and doubly C-labelled acetates and [2- C]- and [2- C]malonates by cultures of Pyrenochaeta 

Although a large number of metabolites appear to be formed by oxidative metabolism of anthraquinones, the cleavage of a benzenoid ring as in phomazarin biosynthesis, rather than the quinonoid ring, is highly unusual. 

Incorporations of [1- Cl- and [ 02]acetates into the novel 9,9 -bianthryl antibiotic setomimycin (79) by cultures of Streptomyces pseudovenezuelae show that (79) is formed by 

Two parallel pathways have been shown to operate simultaneously in the biosynthesis of aurovertins B (80) and D (81) in 

Incorporations of [2- Cjmalonate and [2- C, acetate reveal the absence of an acetate starter unit and so the second pathway involves methylation of a C2Q polyketide precursor at C-18, followed by loss of the chain-initiating acetate unit, C-19—C-20, with the other methyls again derived from methionine. This simultaneous operation of two independent pathways is unique amongst fungal metabolites. 

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The derivation of aflatoxin B can be traced back to the xanthone sterigmatocystin (693), which originates from a decaketide (692), whilst the xanthone bikaverin (694) is derived from a nonaketide. 

ZEA2. ZEA1 produces a nonaketide by using the hexaketide as a starter unit. The nonaketide is easily converted into zearalenone by aromatization and lactonization. 

LNKS formally should synthesize a fully elaborated nonaketide such as 47, which could undergo a biological Diels-Alder reaction to form dihydromonacolin L 48—which is the observed hrst PKS-free intermediate. Note that it is possible that the Diels Alder reaction actually occurs at the more activated hexaketide stage. When lovB was expressed in the heterologous fungal host A. nidulans (4) however, the polyunsaturated compounds... 

Feeding studies to Nocardia argentine sis with - C labelled NAC thioesters of di-, tri-, tetra- and pentaketide intermediates demonstrated regiospecific incorporations into nargenicin 37 (Scheme 18) which are consistent with an intramolecular Diels-Alder cyclisation of a linear nonaketide intermediate (Scheme 19) [72,73]. 

Transformations of cyclic nonaketides by Aspergillus terreus mutants blocked for lovastatin biosynthesis, J.L. Sorensen, K. Auclair, J. Kennedy, C.R. Hutchinson and J.C. Vederas, Org. Biomol. Chem., 2003,1, 50. 

Since we reported the enzymatic activity of SPS in 1995 as the first Diels-Alderase, two additional Diels-Alderases, lovastatin nonaketide synthase (LNKS) and macrophomate synthase (MPS), have been purified and characterized. Two of these catalyze intramolecular Diels-Alder reactions while the third catalyzes an intermolecular Diels-Alder reaction. We have recently reported the detailed reaction pathway ° ° of MPS and its catalytic mechanism based on the crystal structure. " In this section, we describe three natural Diels-Alderases and discuss the mechanism of their catalysis. 

A new nonaketide metabolite, obionin A (28), was isolated as a brownish-red solid from the air-dried mycelium of a halotolerant Ascomycotina, Leptospaeha obiones (Crouan et Crouan) Saccoro (Leptosphaeriaceae), collected from the coastal salt-marsh grass Spartina alternifolia. It constitutes the first reported lH-naphto[2,3-c]pyran 8,9-dione system. The stereochemistry of the side-chain has not yet been determined [76]. 

Later, an extensive study of the biosynthetic pathway involving the incorporation of [ C]acetates and [ C]- and [ C]malonates by cultures of P. terrestris revealed that phomazarin contains nine acetate moieties and must be formed from a single nonaketide chain folded, as shown in Scheme 6 (24). 

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