Lactones from microorganisms

Triacetic acid lactone (1) is one of the simplest polyketides, and its formation from acetyl-CoA and malonyl-CoA has been proved (68JBC5471). Biogenetic formation of triacetic acid lactone has been considered a derailment from fatty acid biosynthesis promoted by the absence of the reductant NADPH (69MII). Pyrone 1 has been isolated from microorganisms (67JA676) and is transformed into tropolone derivatives by Penicillium stipitatum (67JA681). 

Costunolide (165), a very unstable sesquiterpene y-lactone, from Saussurea radix, was treated in Aspergillus niger to produce three dihydrocostunolides (166-168) (Clark and Hufford, 1979). Costunolide is easily converted into eudesmanolides (169-172) in diluted acid, thus 166-168 might be biotransformed after being cyclized in the medium including the microorganisms. If the crude... 

FIGURE 5.13 Formation of lactones by microorganisms. (From Tressl, R., M.Apetz, R. Ar-rieta, K.G. Grunewald, Flavor of Foods and Beverages, G. Charalambous, G.I. Inglett, Eds., Academ. Press, New York, 1978, p. 145. With permission.)... 

Unlike enzymatic reactions, microorganisms have the ability to perform multiple reactions, and they do not require cofacors for regeneration (albeit they require nutrients). They may be used to generate a flavor compound from a nonvolatile precursor (e.g., produce a lactone from castor oil), to effect the bioconversion of one volatile to another (e.g., valencene to nootkatone), or effect a chiral resolution (a racemic mixture of menthol). The primary limitation of using microoganisms for... 

Aluminum chloride s. under Li[AlHJ Microorganisms Optically active lactones from ketocarboxylic acids... 

Indigenous microorganisms obtained from a sandy loam degraded endosulfan to endosulfan diol. This diol was converted to endosulfanhydroxy ether and trace amounts of endosulfan ether and both were degraded to endosulfan lactone (Miles and Moy, 1979). Using settled domestic wastewater inoculum, a-endosulfan (5 and 10 mg/L) did not degrade after 28 d of incubation at 25 °C (Tabak et al, 1981). 

Soil. Metabolites of endosulfan identified in seven soils were endosulfan diol, endosulfanhydroxy ether, endosulfan lactone, and endosulfan sulfate (Martens, 1977 Dreher and Podratzki, 1988). These compounds, including endosulfan ether, were also reported as metabolites identified in aquatic systems (Day, 1991). In soils under aerobic conditions, p-endosulfan is converted to P-endosulfan alcohol and p-endosulfan ether (Perscheid et al., 1973). Endosulfan sulfate was the major biodegradation product in soils under aerobic, anaerobic, and flooded conditions (Martens, 1977). In flooded soils, endolactone was detected only once whereas endodiol and endohydroxy ether were identified in all soils under these conditions. Under anaerobic conditions, endodiol formed in low amounts in two soils (Martens, 1977). Indigenous microorganisms obtained from a sandy loam degraded p-endosulfan to endosulfan diol. This diol was converted to endosulfan a-hydroxy ether and trace amounts of endosulfan ether and both were degraded to endosulfan lactone (Miles and Moy, 1979). 

Pravastatin was isolated as products of enzymatic hydroxylation by some kinds of microorganisms of [lS-[l-a(R ),7p,8P(2S, 4S )8a 3]]-2-methylbutanoic acid l,2,3,7,8,8a-hexahydro-7-methyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2))-pyran-2-yl)ethyl]-l-naphthalenic lactone (campactin) or their carboxylic acid or their salts (products of animal metabolism of microorganisms from the genera Nocardia, Streptomyces et cetera). 

Abamectin is an insecticide/acaricide that contains a mixture of avermectin Bja (>80%) and avermectin Bjb (<20%) as active ingredients. Avermectins, which are macrocyclic lactones, are derived from the actinomycete, Streptomyces avermitilis (soil microorganism). It is used to control insect and mite pests of a wide range of agronomic, fruit, vegetable, and ornamental crops. It is also used by home owners for control of fire ants. It has an oral LD50 in rats of 300 mg/kg. 

Capillary gas chromatographic determination of optical purities, investigation of the conversion of potential precursors, and characterization of enzymes catalyzing these reactions were applied to study the biogenesis of chiral volatiles in plants and microorganisms. Major pineapple constituents are present as mixtures of enantiomers. Reductions, chain elongation, and hydration were shown to be involved in the biosynthesis of hydroxy acid esters and lactones. Reduction of methyl ketones and subsequent enantioselective metabolization by Penicillium citrinum were studied as model reactions to rationalize ratios of enantiomers of secondary alcohols in natural systems. The formation of optically pure enantiomers of aliphatic secondary alcohols and hydroxy acid esters using oxidoreductases from baker s yeast was demonstrated. 

Table 6. The Minimal Inhibitory Concentrations (lig.mT ) of Sesquiterpene Lactones Isolated from T. densum ssp. sivasicum Against a Range of Microorganisms...

Protomycinolide IV (273), a 16-membered macrolide, is isolated from the fermentation broth of the microorganism Micromonospora griseorubida sp. nov. Unique among the medium-sized macrocyclic lactones, it contains three ( )-substituted olefins in addition to six asymmetric centers. The sole synthetic study in this area comes from Yamaguchi s laboratories, as outlined in Scheme 2,23.8 ... 

The polyether nonactin (174) is an antibiotic tetralide produced by the Streptomyces family of microorganisms. From a biological point of view, nonactin and the other compounds in this family of tetrameric lactones have the ablility to strongly complex potassium ion and to facilitate the transport of potassium across membranes by providing a lipophilic shell. Ion transport has been shown to have a strong influence on important biological functions such as oxidative phosphorylation and mitochondrial respiration. 

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