Streptomyces fulvissimus

These substances include primarily depsipeptides (compounds whose structural units consist of alternating amino acid and ar-hydroxy acid units). Their best-known representative is the cyclic antibiotic, valinomycin, with a 36-membered ring [L-Lac-L-Val-D-Hy-i-Valac-D-Val]3, which was isolated from a culture of the microorganism, Streptomyces fulvissimus. Figure 6.13 depicts the structure of free valinomycin and its complex with a potassium ion, the most important of the coordination compounds of valinomycin. 

Attention has already been made to the formation of glycoside and sulfate conjugates of phenolic metabolites during the biotransformation of polycyclic aromatic hydrocarbons by fungi (Section 6.2.2). Formation of sulfate esters is not, however, limited to fungal systems since this has been observed, for example, following 4 -hydroxylation of 5-hydroxyflavone in Streptomyces fulvissimus (Ibrahim and Abul-Hajj 1989), and the enzyme has been partly purified from a Eubacterium sp. (Koizumi et al. 1990). 

Ibrahim, A.-R. and Y.J. Abul-Hajj. 1989. Aromatic hydroxylation and sulfation of 5-hydroxyflavone by Streptomyces fulvissimus. Appl. Environ. Microbiol. 55 3140-3142. 

C54H 40 g, Mr 1111.34, cryst., mp. 187°C, [a]p +31° (benzene), soluble in organic solvents. Cyclodep-sipeptide antibiotic from Streptomyces fulvissimus structurally related to the enniatins. V. is composed of three residues each of L- valine, D-valine, D-a-hy-droxyisovaleric acid, and L- lactic acid that form a 36-membered ring. V. is active against the tuberculosis pathogen (Mycobacterium tuberculosis). LD50 (rat p.o.) 4 mg/kg, it is highly toxic when swallowed or on contact with the skin. 

In 1955, H. Brockmann and Schmidt-Kastner [15] isolated an antibiotic substance from extracts of Streptomyces fulvissimus. They named it valinomycin after valine having been found as the only amino acid in the acid-hydrolyzate. Since no amino group nor carboxyl group could be detected in the substance which was almost insoluble in water, a cyclic structure had to be assumed. Valinomycin has a macrocyclic molecular structure consisting of three identical tetradepsipeptide fragments with alternating peptide and ester bonds between D-a-hydroxyisovaleric acid, D-valine, L-lactic add, L-valyl residues (Fig. 10). 

FIGURE 20.74 Biotransformation of parthenolide (240) and its dihydro derivative (247) by Rhizopus nigricans, Streptomyces fulvissimus, and Rhodotorula rubra. 

Galal et al. (1999) reported that Streptomyces fulvissimus or Rhizopus nigricans converted parthenolide (240) into lla-methylparthenoUde (247) in 20-30% yield while metabolite lip-hydroxyparthenoUde (248) was obtained by incubation of 240 with Rhizopus nigricans and... 

Rhodotorula rubra. In addition to the metabolite 247, Streptomyces fulvissimus gave minor polar metabolite, 9P-hydroxy derivative (248a) in low yield (3%). The same metabolite (248a) was obtained from 247 by fermentation of Streptomycesfulvissimus as a minor constituent. Furthermore, 14-hydroxyparthenolide (248b) was obtained from 240 and 247 as a minor component (4%) by Rhizopus nigricans (Figure 15.74). 

Several fungal metabolites have been found which enhance the passive uptake of potassium. Some, like nonactin and monactin (14.5), are macro-tetrolides others, like valinomycin, are depsipeptides. Valinomycin (from Streptomyces fulvissimus) is a macrocycle (mol. wt. iii) composed of three residues of each of L-valine, d-valine, L-lactic acid, and D-a-hydroxy-/swaleric acid, linked alternately by ester and amide bonds to form a 36-membered ring (Shemyakin et al.y 1963). It is soluble in lipids but... 

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