Penicillia

The first penicillin was benzylpenicillin (penicillin G, R = C6H5 CH2 C0 NH-), which is made by growing suitable strains of Penicillium chrysogenum on a carbohydrate medium. 

Under natural conditions various strains of Penicillium fungi produce either penicillin G or free 6-aminopenicillanic add ( = 6-APA). The techniques used to prepare analogues such as the ones given above have been (i) fermentation in the presence of an excess of appropriate adds which may be incorporated as side-chain (ii) chemical acylation of 6-APA with activated acid derivatives. 

APA may be either obtained directly from special Penicillium strains or by hydrolysis of penicillin Q with the aid of amidase enzymes. A major problem in the synthesis of different amides from 6-APA is the acid- and base-sensitivity of its -lactam ring which is usually very unstable outside of the pH range from 3 to 6. One synthesis of ampidllin applies the condensation of 6-APA with a mixed anhydride of N-protected phenylglydne. Catalytic hydrogenation removes the N-protecting group. Yields are low (2 30%) (without scheme). 

Lactic acid-producing bacteria associated with fermented dairy products have been found to produce antibiotic-like compounds caUed bacteriocins. Concentrations of these natural antibiotics can be added to refrigerated foods in the form of an extract of the fermentation process to help prevent microbial spoilage. Other natural antibiotics are produced by Penicillium wqueforti the mold associated with Roquefort and blue cheese, and by Propionibacterium sp., which produce propionic acid and are associated with Swiss-type cheeses (3). 

Gestodene has been prepared in several ways (85). The route that provides the highest yield is shown in Eigure 8. Microbial oxidation of (55) with Penicillium raistrickii results in the 15-alcohol (56). Protection of the alcohol as the acetate (57) and protection of the ketone as a dienolether provides (58). In a one-pot procedure (58) is treated with lithium acetyUde and subjected to a hydrolytic work-up to provide gestodene (54) (86). 

In addition to its presence in fmits, S(—)-malic acid has been found in cultures of a variety of microorganisms including the aspergiUi, yeasts, species of Sekrotinia, and Penicillium brevicompactum. Yields of levorotatory malic acid as high as 74% of theoretical have been reported. Iron, manganese, chromium, or aluminum ions reportedly enhance malic acid production. S(—)-Mahc acid is involved in two respiratory metaboHc cycles the Krebs tricarboxylic acid... 

Griseofulvia [126-07-8] (54) coataias the pblorogluciaol aucleus. It is an important oral antifungal agent ia humans and animals, elaborated by certain strains of Penicillium. One synthesis of griseofulvia is based oa the appropriately substituted pblorogluciaol (196). Uvaretia [58449-06-2] (55), which is extracted from JJvaria acuminata inhibits lymphocytic leukemia (200). 

Penicillins. Since the discovery of penicillin in 1928 as an antibacterial elaborated by a mold, Penicillium notatum the global search for better antibiotic-producing organism species, radiation-induced mutation, and culture-media modifications have been used to maximize production of the compound. These efforts have resulted in the discovery of a variety of natural penicillins differing in side chains from the basic molecule, 6-aminopenici11anic acid [551-16-6], These chemical variations have produced an assortment of dmgs having diverse pharmacokinetic and antibacterial characteristics (see Antibiotics, P-lactams). 

Fig. 1. Biosynthesis of cephalosporins and cephamycins. a, Cephalosporium acremonium, b, Penicillium chjsogenum, c, Streptomjces clavuligerus-, d, Streptomjces lipmanir, e, Streptomjces wadajamensis, REX is a ring expansion en2yme (deacetoxycephalosporin C synthethase).

Fleming s serendipitous observation of the lysis of staphylococcus colonies in the vicinity of Penicillium notatum 29MI51100). 

The mold metabolite mycelianamide, isolated from the mycelium of strains of Penicillium gritieofulvum Dierckx, was first investigated by Oxford and Raistrick. The reinterpretation and extension of this work by Birch et and the revision by Bates et of the structure first proposed for the terpenoid side-chain, have led to the formulation of mycelianamide as 11. This structure has been confirmed by further degradations and by a synthesis of racemic deoxymyceli-anamide by Gallina and co-workers. The ready decomposition of the heterocyclic ring by either acid or alkali is discussed later (Section... 

Research on novel fungal secondary metabolites resulted in the isolation of an interesting spiran, griseofulvin (15), from fermentation beers of the mold Penicillium griseofulvum. 

The nature of the penicillin derivatives accessible by this "feeding" route was severely limited by the fact that the acylat-ing enzyme of the Penicillium molds would accept only those carboxylic acids which bore at least some resemblance to its natural substrates. A breakthrough in this field was achieved by the finding that rigid exclusion of all possible side-chain substrate from the culture medium afforded 6-APA as the main fermentation... 

Pinselschimmel, m. any species of Penicillium. Pinusharz, n. pine resin. 

The first organism reported to produce poly(L-malic acid) was Penicillium cyclopium [7]. An amount of 2.6-... 

Peanut oil, composition of, 1062 Pedersen, Charles John, 666 Penicillin, discovery of, 824-825 Penicillin V, specific rotation of, 296 stereochemistry of, 321 Penicillium notation, penicillin from. 824... 

Penicillins, like most antibiotics, are secondary products whose synthesis is not directly linked to growth. The enzymes that produce secondary products are normally repressed or inhibited under conditions which favour rapid growth. In the early work on penicillin, Penicillium rwtatum was grown as a floating mycelium on about 2 cm depth of liquid medium. The mycelium absorbed nutrients from the medium and penicillin was excreted into the medium. The mycelium and spent medium are readily separated. 

---