Xanthofulvin, a novel semaphorin inhibitor produced by a strain of Penicillium

A new semaphorin inhibitor xanthofulvin was isolated from the cultured broth of a fungus Penicillium sp. SPF-3059 along with a known compound vinaxanthone by solvent extraction and bioassay-guided fractionation. The tautomeric structure of xanthofulvin was determined by spectroscopic analyses. The two compounds exhibited significant semaphorin inhibitory activity with IC50 values of 0.09 and 0.1 microg/ml, respectively, in semaphorin3A-induced growth cone collapse assay using cultured chick dorsal root ganglia neurons.     

Safety evaluation of phosphodiesterase produced from Penicillium citrinum: summary of toxicological data

The toxicity of Enzyme RP-1, an enzyme preparation used to hydrolyze yeast RNA to produce flavor enhancers for use in the food industry, was evaluated in a series of studies. A 5-week dietary toxicity study in Wistar rats was conducted in which animals received Enzyme RP-1 in feed at concentrations of 0, 500, 2000, or 8000 mg/kg body wt/day. A 13-week dietary toxicity study in Sprague-Dawley rats was conducted in which animals received RP-1 concentrate at 0, 0.125, 0.5, or 2% in their diets. At the highest dose levels in both studies, submandibular glands in the oral cavity were enlarged, an effect attributed to protease activity of the enzyme preparation. The no-observed-effect level in rats in the 13-week study was 0.5%, equivalent to 317 mg/kg body wt/day for males and 346 mg/kg body wt/day for females. Based on estimated dietary exposure to the enzyme preparation, the margin of exposure is estimated to be greater than 38,000. Lack of genotoxic potential was demonstrated by an in vitro reverse mutation assay in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and in Escherichia coli strain WP2uvr and by an in vitro chromosome aberration test in CHL/IU cells derived from fibroblasts from the lungs of Chinese hamsters. Finally, the particular strain of Penicillium citrinum, the fungal strain used to prepare Enzyme RP-1, was shown to have low pathogenicity upon a single injection into the tail vein of rats of viable spores at doses up to 2.8x10(5) colony-forming units per animal. The results of these studies demonstrate that the enzyme preparation may be considered safe to workers and consumers when employed in the production of flavor enhancers from yeast.     

产紫青霉G59的庆大霉素抗性突变株新产抗肿瘤活性产物研究

目的阐明真菌无活性野生株产紫青霉G59的庆大霉素抗性突变株2-5-3-1新产抗肿瘤活性产物。方法在活性跟踪和薄层检测指导下,通过与原始菌样品直接对照,利用液液萃取、柱层析、制备薄层层析、重结晶等技术,分离纯化活性产物。根据理化常数和波谱数据鉴定化合物结构。用MTT法测试样品对K562细胞的抑制活性。结果从突变株2-5-3-1发酵物中分离鉴定了麦角甾醇（1）、fructigenine A（2）、rugulosuvine A（3）、大黄素（4）和ω-羟基大黄素（5）。化合物1~5在100μg/ml浓度下对K562细胞的抑制率分别为52.8%、60.8%、41.2%、84.6%和37.1%,其中1、2和4的IC50分别为93.1、58.4和30.0μg/ml。结论化合物1~5均为产紫青霉G59不生产而突变株新产抗肿瘤活性产物。用DMSO介导的庆大霉素抗性筛选方法可以将无活性真菌野生株转化成活性突变株并供新产活性产物研究。     

霉酚酸产生菌短密青霉菌UA-32的发酵研究

研究短密青霉菌UA-32产生霉酚酸的发酵条件。改良了种子培养基,并对发酵所需的氨基酸、碳源进行了考察;采用正交设计优化得到发酵培养基配方。优化后的摇瓶发酵单位比优化前提高90%。     

产紫青霉G59的两株突变株新产抗肿瘤活性产物研究

目的阐明无活性真菌产紫青霉G59的两株抗肿瘤活性突变株2-2-3和PDN-f-2新产活性产物。方法采用与原始菌样品直接对照和活性跟踪分离的实验模式,利用液液萃取、柱层析、重结晶等方法分离纯化活性产物。利用现代波谱技术鉴定化合物结构。用MTT法测试样品对K562细胞的抑制活性。结果从2-2-3和PDN-f-2发酵物中分别分离鉴定了ergone（1）和citrinin（2）。化合物1和2抑制K562细胞的IC50分别为7.4和48.0μg/ml。结论化合物1和2均为产紫青霉产物中未见报道的G59的两株突变株新产活性产物。将无活性真菌野生株转化成活性突变株并研究其新产活性产物,将有可能成为拓展药源真菌活性菌株新资源的很好途径。     

Deoxyverrucosidin, a novel GRP78/BiP down-regulator, produced by Penicillium sp

Glucose-regulated protein 78 (GRP78) resides in endoplasmic reticulum (ER) and plays a role in protecting tumor cells against the toxic effects of anticancer agents. During the search for down-regulators of GRP78 using a reporter gene (luciferase) assay system, we isolated a novel compound designated as deoxyverrucosidin (1), a congener of verrucosidin (2), from Penicillium sp. and identified it as a down-regulator of the grp78 gene. The structure of 1 was determined by mainly ESI-mass and two-dimensional NMR spectra. 1 dose-dependently inhibited the expression of GRP78 promoter with an IC50 of 30 nM.     

Penitricin, a new class of antibiotic produced by Penicillium aculeatum. IV. Biosynthesis

Bioconversion experiments using washed mycelia of Penicillium aculeatum NR 5165 and NR 6216 revealed that penitricin (Ro 09-0804, hydroxymethylcyclopropenone) was biosynthesized from trans-2-butene-1,4-diol via 4-hydroxycrotonaldehyde.     

Herquline, a new alkaloid produced by Penicillium herquei. Fermentation, isolation and properties.

A new alkaloid named herquline has been isolated from culture broth of Penicillium herquei Fg-372 by solvent extraction and silica gel chromatography. The molecular formula of herquline has been determined as C19H26N2O2 on the basis of elemental analysis and its high resolution mass spectrometry. The compound does not possess antimicrobial activities, but weakly inhibits blood platelet aggregation induced by adenosine diphosphate.     

Penitricin, a new class of antibiotic produced by Penicillium aculeatum. II. Isolation and characterization

A novel antibiotic, penitricin, Ro 09-0804, has been produced in the culture filtrate of Penicillium aculeatum NR 5165. This antibiotic was purified by repeated extraction of culture filtrate with 1-butanol, and passage of the crude extracts through Sephadex G-10, followed by HPLC (Shodex Ionpak S-801). Physico-chemical characterization was made on penitricin, while two open-ringed penitricins B and C co-produced by the producer strain were also identified.     

Two new meroterpenoids produced by the endophytic fungus Penicillium sp. SXH-65

Two new meroterpenoids, arisugacins I (1) and J (2), together with five known meroterpenoids including arisugacin B (3), arisugacin F (4), arisugacin G (5), territrem B (6) and territrem C (7) were isolated from an endophytic fungus Penicillium sp. SXH-65. Their structures were determined by extensive spectroscopic experiments and comparison with literature data. Their cytotoxicities were evaluated against Hela, HL-60 and K562 cell lines, and only 3 and 4 exhibited weak cytotoxicities against Hela, HL-60 and K562 cell lines with IC₅₀ values ranging from 24 to 60 μM.     

Hepatic alterations produced in mice by xanthomegnin and viomellein,metabolites of Penicillium viridicatum

Xanthomegnin and viomellein obtained from a toxigenic isolate of Penicillium viridicatum were fed to weanling male Swiss mice at dietary concentrations of 448 and 456 mg/kg of feed, respectively. Gross alterations included jaundice, greenish discoloration of the kidney, and small foci of discoloration in the liver. The histologic alterations in the liver were centered about the intrahepatic biliary ducts and included necrotizing cholangitis, periductal edema and pericholangitis, disseminated focal hepatic necrosis, periductal fibrosis, and hypertrophy and hyperplasia of biliary epithelium. The spectrum of hepatic lesions were as previously produced in mice by crude cultural products of P. viridicatum.     

之江菌素的毒性实验

之江菌素对ＩＣＲ小鼠灌胃，ＬＤ５０为１１５３．８ｍｇ／ｋｇ，属低毒物质。致畸致突变试验阴性。亚慢毒性试验表明，大鼠饲喂含之江菌素４００ｐｐｍ的饲料连续２８ｄ，对生长发育、饲料利用率、血液及生化指标、病理组织学观察均无明显不良影响