K-582, a new peptide antibiotic. I.

Abstract

A new basic peptide antibiotic designated as K-582 was isolated, purified and characterized. When K-582 was applied to a column of A1203 or Bio-Gel P-2 or CM Sephadex, two major peaks which were named Fraction I (K-582 A) and Fraction II (K-582 B) were obtained. The nitrogen content, the behavior in color reaction, the absorption bands of amide linkages in the infrared absorption spectrum, 1H NMR spectrum and C-13 NMR spectrum indicated the peptide nature of K-582 A and K-582 B. K-582 was effective against yeasts, but inactive against other Gram-positive bacteria, Gram-negative bacteria and Mycobacterium. The toxicity was low in mice.During our screening program for substances with antibiotic activity, we found a new substance named K-582 produced by the strain 582M which was isolated from a soil sample collected in Sendai and from the results of detailed taxonomical studies the strain was identified as Metarhizium anisopliae (METSCH.) SOROK. Var. anisopliae.The antibiotic, K-582, exhibited a significant growth inhibition of Candida in liquid media, of viruses in tissue culture and of ascites tumor in mice.This paper deals with the characterization of Metarhizium anisopliae (METSCH.) SOROK. var. anisopliae 582 M, the fermentation process, the isolation procedure and the properties of K-582. Taxonomical StudiesStrain 582 M was isolated by SHIGEJI KONDO from a soil sample collected in the vicinity of Sendai City, Miyagi Prefecture, Japan. The taxonomical characterization was carried out according to the methods described by BARNETT1), BARRON2) and TULLOCH3) and the strain 582 M was classified as Metarhizium anisopliae (METSCH.) SOROK. var. anisopliae. Macroscopic descriptionColonies on CZAPEK-peptone agar grew rapidly, attaining a diameter of 4.5 -5.0 cm in 2 weeks at 28°C. The colonies are more or less fasciculated, plane or sometimes lightly furrowed radially. They have white margins with olivaceous to dark olivaceous colored sporulating areas in center. Colonies are often intermixed or zonate. Transformation to light yellow to dark olivaceous colors occurs. Exudate is lacking. The odor was conspicuously pungent similar to that of streptomyces (Tables 1, 2 and 3.).

Fungal tyrosine betaine, a novel secondary metabolite from conidia of entomopathogenic Metarhizium spp. fungi

“…produce a variety of secondary metabolites in several chemical classes, including cytochalasins C and D (Aldridge & Turner 1969), myroridins (Kondo et al 1980), destruxins A, B andE (Roberts 1969;Païs et al 1981), viridoxin (Gupta et al 1993), swainsonine (Patrick et al 1993), helvonic acid (Espada & Dreyfuss 1997), 12-hydroxyovalicin (Kuboki et al 1999), hydroxyfungerin, 7-desmethyl analogues of fusarin C and (8Z)-fusarin C (Krasnoff et al 2006), serinocyclins A and B (Krasnoff et al 2007) and aurovertins (Azumi et al 2008). M. anisopliae metabolites are toxic to a broad range of animals and microbes, including insects (Gupta et al 1989;Roberts et al 1992;Vilcinskas et al 1997;Roberts & St. Leger 2004;Pal et al 2007), fungi, bacteria and viruses (Kondo et al 1980;Krasnoff et al 2006). Most of these metabolites were isolated from mycelia or from fermentation extracts.…”

Agrobacterium -Mediated Disruption of a Nonribosomal Peptide Synthetase Gene in the Invertebrate Pathogen Metarhizium anisopliae Reveals a Peptide Spore Factor

“…Furthermore, in vitro assays utilizing purified destruxins have demonstrated a wide range of biological activities against insects, including immunosuppression, activation of calcium channels in muscle, antifeedant activity, and acute toxicity (28,57,60,66,67,75,81). M. anisopliae also produces the myroridin antibiotics (44), which are linear heptapeptides that show antifungal and antiviral activities, as well as cell growth inhibition (32).…”

Production of Mutagenic Metabolites by Metarhizium anisopliae

“…Metarhizium species produce a variety of secondary metabolites, preeminently the destruxins, cyclic depsipeptides possessing a broad range of toxic effects, including acute toxicity to insects (5)(6)(7). Metabolites reported to date from Metarhizium species include cytochalasins C and D (8), helvolic acid (9), swainsonine (10), 12-hydroxyovalicin (11), viridoxin (12), myroridins (13), and hydroxyfungerin (14).…”

“…Compound 2 (NG-393): yellow oil; [R] 25 D 181.6°(c ) 2.7 mg/ mL, MeOH); HPLC tR ) 8.9 min; HRESI-MS m/z [M + H] + 418.1859 (calcd for C22H28NO7, 418.1866). For 1 H NMR, 13 C NMR, HMBC, COSY, and NOESY data, see Table 1, Figure 2, and the Supporting Information.…”