From Streptomycetes

Ubenimex, [(2(3),3(R))-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, was isolated as an inhibitor of aminopeptidases, on which it acts as a strong, reversible transition-state analogue inhibitor (293). Analogues of ubenimex have been made and some other aminopeptidase inhibitors, not all of them peptides, have been isolated from streptomycetes (294—296). 

Secondary metabolites generated via the propionate route are quite unusual in nature. Relevant exceptions are some antibiotic macrolides from Streptomycetes [42], but wholly propionate-derived macrolides are rare. This biosynthetic pathway has been well proved for erythromycin (13), where the aglycone is produced by assembling seven propionate units [43, 44], and for a few related antibiotics [45]. However, very sophisticated biosynthetic experiments [46] have established that some apparent propionate units in other macrolides (e.g., aplasmomycin [46]) from Streptomycetes could be formed either by C-methylation through S-adenosylmethionine or from glycerol. 

Isolated from Streptomycetes Antibacterial and antifungal amino 90... 

It was shown later that the streptomycete can only modify rather than biosynthesize these compounds [66] and that all such derivatives, i.e. even genisteins (64,65) come from the soy meal or cotton seed and are not produced by streptomycetes. These results demonstrate clearly that flavonoids isolated from streptomycetes cultivated on media containing plant components, such as soy meal or cotton seed, always come from the cultivation medium and are not of microbial origin. The same effect was observed in S. griseus [65] producing two additional chlorinated genisteins (66,67). This also holds true [67] for isoflavone (68) isolated from Japanese soil. 

The antibiotic nybomycin (290 R = OH), 8-hydroxymethyl-6-methyl-2/Tr,4jFTr-oxazolo[5,4,3-//]pyrido[3,2-g]quinolin-4-one, is active against Gram-positive and some Gram-negative bacteria. It was isolated from streptomycete cultures and together with deoxynybomycin (290 R=H) it is available by synthesis (73JA5003). 

The 1,3-anti -reduction of (3-hydroxy ketones was utilized in the total synthesis of (+)-roxaticin (14), a pentaene macrolide isolated from streptomycete X-149944 (Scheme 4.2e). The (3-hydroxy ketone 15 underwent 1,3-anti -reduction to afford the diol 16 in 99% yield and greater than 95 5 diastereoselectivity. The resulting diol was then protected as a cyclopentylidene ketal (17) by using cyclopentylidene dimethyl ketal and pyridinium p-toluene sulfonate (PPTS). 

VALERIA CALI, CARMELA SPATAFORA AND CORRADO TRINGALl 263 Halogen-Containing Antibiotics from Streptomycetes... 

Arcyria pigments (bisindolylmaleimides and in-dolo[2,3-a]carbazoles). The tiny fruit bodies of the slime molds Arcyria denudata, A. nutans, and related myxomycetes contain indole pigments of the bisindol-ylmaleinimide type. Parent compounds are the red ar-cyriarubins A, B, and C. Oxidative cyclization in the 2,2 -position furnishes the pale yellow and poorly soluble arcyriaflavins A, B, and C (table I). Indolocarba-zoles of this type are also known as active principles from streptomycetes ( rebeccamycin). 

International generic name for an anthracycline antibiotic from streptomycetes (e.g., Streptomyces peu-cetius). C27H29NO10, Mr 527.53, hydrochloride red needles, decomp. >177 C. Acidic hydrolysis of D. furnishes L-daunosamine and the aglycone daunomyci-none Cj.HigOg, Mr 398.37, mp. 213-214°C, [aJi, +193 (dioxane). ... 

Antifungal and cytotoxic a-methoxy-y-pyrone derivative from Polyangium sp. (Myxobacteria), f-ssHasNOa Mr 379.46. P. crystallizes from butyl methyl ether as colorless crystals with mp. 92-93°C, uv,, 244 nm, 252 nm. The pyrone part of P. has a close relationship to aureothin and spectinabilin from streptomycetes. In addition to the antifungal activity, e.g., against Us-tilago maydis (MHK 19 pg/L) a cytotoxic activity has also been observed which mimics an antiviral activity in cellular assays. The reason for this is an inhibition of NADH ubiquinone oxidoreductase in complex I of the respiratory chain. 

Streptothricins. A mixture of antibiotics of the nucleoside type first isolated in 1942 by Waksman and Woodruff from streptomycetes. S. were first considered to be a uniform substance and given the name S. F. The mixture was later found to consist of several, frequently occurring compounds that differ in the number of /3-lysine units in the side chain. 

In the 1970s and the 1980s, the pathways to the penicillins and the cephalosporins including cephamycin C were worked out especially after cell-free systems became available [59]. Late in the 1970s came reports on the production of P-lactam antibiotics which were neither penicillins nor cephalosporins. The most important was clavulanic acid from streptomycetes, which possessed only weak antibiotic activity but was an excellent inhibitor of P-lactamase [60]. It became a blockbuster compound by being coformulated with broad-spectrum semisynthetic penicillins which are susceptible to P-lactamase, for example, with amoxycillin, the combination is known as Augmentin. 

---