Occurrence and Chemical Synthesis of Apocarotenoids from Mucorales: A Review.

Apocarotenoids are metabolites originated by degradation of carotenes through the loss of carbon atoms placed at the side chain of their structure as consequence of oxydative reactions. We present here the first review of apocarotenoids in the fungi mucorales Phycomyces blakesleeanus, Blakeslea trispora and Mucor mucedo. This review is divided into two parts: the first one presents their structures and sources, whereas the second part is dedicated to their chemical synthesis.

Unusual microbial lactonization and hydroxylation of asiatic acid by Umbelopsis isabellina.

Asiatic acid (1) is a natural triterpenoid isolated from Centella asiatica. This paper reports the microbial transformation of asiatic acid by an endophytic fungus Umbelopsis isabellina to obtain derivatives potentially useful for further studies. Incubation of asiatic acid with U. isabellina afforded two derivatives 2α,3ß,7ß, 23-tetrahydroxyurs-12-ene-28-oic acid (2) and 2α,3ß,7ß,23-tetrahydroxyurs-11-ene-28,13-lactone (3). The structures of these compounds were elucidated by spectral data. Compound 3 has formed an unusual lactone. These two products are new compounds. The possible transformation passway was also discussed.

Bioactive depsidones from the fungus Pilobolus heterosporus.

A new aromatic ester, pilobolusate (1), four new depsidones, pilobolusones A-D (2-5), five known depsidones, (6-10), and ergosterol were isolated from the fungus Pilobolus heterosporus. Their structures were established on the basis of spectroscopic data. Compounds 2 and 4-9 showed cytotoxicity against three cancer cell lines (KB, MCF-7, and NCI-H187) with IC50 values in the range of 9.94-97.42 µM. In addition, compounds 2, 5, 9, and 10 exhibited antimalarial activity against Plasmodium falciparum with IC50 values ranging from 3.67-23.56 µM.

Anti-aging effect of Blakeslea trispora powder on adult mice.

Blakeslea trispora powder that contains 1.9 % lycopene was tested for its anti-aging effect on adult mice. 48 adult mice were administered with the powder at 0, 267, 534, 1,068 mg lycopene kg(-1) body daily for 30 days. The body weight, hematology, clinical chemical and antioxidant activities in major organs of adult mice were measured. The powder had no effect on the body weight, hematology, clinical chemical parameters of adult mice but improved the antioxidant activities in major organs of adult mice. Increased activities of superoxide dismutase, catalase and glutathione peroxidase and a decreased amount of malondialdehyde in liver, brain, kidney and skin of adult mice when a high-dose of the B. trispora powder was administered, suggests that it has the ability to enhance the antioxidation system and improve the anti-aging abilities of adult mice.

Indigenous to Tanzania.

The objective of this study was to evaluate free radical scavenging capacity of crude extracts from forest basidiomycetous fungi, domestic zygomycetous fungi and marine ascomycetous fungi. Lethal concentration values that kill 50% of the brine shrimps (LC50) were determined from 19 fungal extracts using brine shrimp test (BST). The LC50 values of fungal extract ranged between 0.28-40 µg/ml. The basidiomycetous (Lactarius volemoides) was the most toxic fungi with LC50 of 0.28 µg/ml while ascomycete Pichia guilliermondii showed the least toxicity with LC50 of 40 µg/ml. The concentrations of eleven fungal extracts were further evaluated on their ability to scavenge free radical using 1-diphenyl-2-picrylhydrazyl (α,α-diphenyl-ß-picrylhydrazyl) (DPPH) as a dye reagent for spectrophotometric assay at 517 nm. The extract concentrations that decreased the initial DPPH radical by 50% (EC50) were determined. The EC50 values ranged from 19-60.4 µg/ml ascorbic acid equivalents. Extracts from an edible but undomesticated basidiomycetous fungus isolated from Miombo forest and identified as Termitomyces microcarpus showed the highest scavenging effect with EC50 at 19 µg/ml while that from ascomycete Candida tropicalis showed the least EC50 at 60.4 µg/ml. These results draw attention to wild undomesticated Miombo fungi as potential source of nutritional supplements worth further investigation.

Lycopene absorption in humans after the intake of two different single-dose lycopene formulations.

Lycopene is the main carotenoid present in tomato and its derivatives. It can also be obtained from the fungus Blakeslea trispora and its use as novel food ingredient was recently approved. The aim of the present study was to investigate the absorption of lycopene, in humans, after the intake of a single dose providing 15mg of lycopene from tomato extract (oleoresin 6%) or B. trispora (oil suspension 6%). Twelve female subjects were enrolled and divided into two groups: group 1 was assigned to the sequence tomato lycopene/wash-out/B. trispora lycopene, whereas group 2 followed the sequence B. trispora lycopene/wash-out/tomato lycopene. The formulations were consumed early in the morning with 5mL of sunflower oil, 100g of bread and 150mL of water. Blood was collected before consumption and after 2, 4, 6, 8, 10, 12 and 24h. Plasma lycopene concentrations were determined by HPLC analysis. On the whole, statistical analysis of data did not demonstrate a different effect of the type of lycopene source on the carotenoid absorption. The maximum increase in plasma lycopene concentration was about 40nmol/L for both products at 10-12h (p<0.05) post-consumption and decreased to basal values at 24h. A transient higher increase in lycopene concentration at 4-6h (p<0.05) after tomato lycopene with respect to B. trispora lycopene intake was observed. In conclusion, the intake of a single dose of the two liposoluble lycopene formulations revealed a comparable, small, but significant increase in plasma lycopene concentrations.

Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats.

Lycopene, as a suspension in sunflower oil (20% w/w), was tested for subchronic toxicity by administration at dietary concentrations of 0, 0.25, 0.50, and 1.0% to groups of 20 male and 20 female Wistar rats for a period of 90 days. The lycopene examined in this study was derived from a fungal biomass (Blakeslea trispora). Lycopene intake was calculated to be 0, 145, 291, and 586mg/kg body weight/day in control through high-dose males and 0, 156, 312, and 616mg/kg body weight/day in control through high-dose females. The results from this study do not provide any evidence of toxicity of lycopene at dietary levels up to 1.0% as demonstrated by the findings of clinical observations, neurobehavioral observations, motor activity assessment, body weight and food consumption measurements, ophthalmoscopic examinations, hematology, clinical chemistry, urinalysis, organ weights, gross pathology, or histopathology. The No-Observed-Effect Level (NOEL) was 1.0% in the diet, the highest dietary concentration tested.

Preliminary safety assessment of an arachidonic acid-enriched oil derived from Mortierella alpina: summary of toxicological data.

An arachidonic acid-enriched oil (AA-oil), derived from Mortierella alpina was subjected to a programme of studies to establish its preliminary safety for use in infant nutrition. This was addressed at two levels: (1) HPLC analysis of metabolites produced by the production strains at various conditions, and (2) an evaluation of the toxicity of the final product. The following studies were carried out on the AA-oil: gene mutation assays in bacteria and mammalian cells in vitro; chromosome aberration assays both in vitro and in vivo and acute and subacute (4-wk) oral toxicity in the rat. No known mycotoxins were produced by the production strains under the conditions tested. Further, the oil did not show mutagenic or clastogenic activity and the acute oral toxicity, expressed as the LD50 value, exceeded 20 ml/kg body weight, that is, 18.2 g/kg body weight. In the subacute oral toxicity study the AA-oil was tested as such and in combination with a docosahexaenoic-enriched oil (DHA-oil) derived from fish oil at a ratio of 2:1 (AA:DHA). This was done because high dose levels of AA may result in adverse effects; DHA can compensate for these effects. Furthermore, human milk contains both AA and DHA at a ratio of AA:DHA of 2 to 3:1. No obvious signs of toxicity were observed. Levels of phospholipids and triglycerides tended to be decreased in the highest dose groups. The no-observed-adverse-effect level of the AA-oil in the subacute 4-wk toxicity study was placed at the highest levels tested, namely 3000 mg AA-oil/kg body weight/day as such and in the combination of 3000 mg AA-oil and 1500 mg DHA-oil/kg body weight/day. This corresponds to an intake of 1000 mg AA/kg body weight/day, which represents approximately 37 times the infant intake of AA in human milk.

Evaluation of single cell sources of docosahexaenoic acid and arachidonic acid: a 4-week oral safety study in rats.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are secreted in human milk and consumed by the nursing neonate but are not present in infant formulas currently available in the US. Supplementation of formulas with DHA and ARA may be particularly important for premature infants, who have less accretion of these fatty acids in utero than term infants. Some experts suggest that DHA and ARA should be added to infant formulas. Common sources of these fatty acids (e.g. fish oils, egg yolk lipids) are not optimal for infants in that they contain disproportionate amounts of other fatty acids. This 4-wk study examined the safety of a high-DHA algal oil and a high-ARA fungal oil, blended so that the DHA:ARA ratio approximates that in human milk. Rats were fed the blend at levels representing three, 11 and 22 times the anticipated infant exposure. Control animals were fed either a high-fat diet (13.1%, w/w; equivalent to the fat content of the treated groups) or a low-fat diet (5%, w/w). There were no treatment-related differences in body weight, food intake, organ weights, haematology or clinical chemistry. Thus, this study indicates that a blend of algal and fungal oils is a safe source of DHA and ARA as it produced no adverse effects in rats when administered for 4 wk at levels up to 22 times the expected infant exposure.