Penicillium diversion

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). 

Collie s hypothesis that aromatic compounds are made biologically from ethanoic acid was greatly expanded by A. J. Birch to include an extraordinary number of diverse compounds. The generic name acetogenin has been suggested as a convenient classification for ethanoate (acetate)-derived natural products, but the name polyketides also is used. Naturally occurring aromatic compounds and quinones are largely made in this way. An example is 2-hydroxy-6-methylbenzoic acid formed as a metabolite of the mold Penicillium urticae ... 

Metabolites of the ergoline type [as (128)], as well as those of type (119), have been isolated from Penicillium roqueforti. The incorporation has been observed of radioactive samples of tryptophan and mevalonate into both series of metabolites, and of histidine into those of type (119).44 Diversion from tryptophan into the two independent biosynthetic pathways is initiated on the one hand by the formation of (122) and on the other by reaction with histidine to give a diketopiperazine precursor for metabolites such as (119). Which route is followed is temperature-dependent. 

This is an amazing array of diverse metabolites produced by four species of Penicillium, isolated from a tiny piece of bark from a single yew tree. Can these phenomenal chemists be induced to synthesize ever more unique metabolites with desirable biological activities ... 

The proliferation in the number of new and diverse fungal metabolites in recent years complicates a comprehensive survey of their biogenetic origin. The biosynthesis of many metabolites appears to be trivial, because a cursory chemical inspection of the structure allows the formulation of a plausible biosynthetic pathway. For many new metabolites, no toxicological data are available and only the structural elucidation together with a biosynthetic postulate is reported. Thus the biosynthetic origin of viridicatumtoxin (1), a toxic metabolite from Penicillium viridicatum (Kabuto et al., 1976), has not been studied, but is most probably closely modeled on that of the tetracyclines (McCormick, 1967). Similarly, verruculotoxin (2), isolated from cultures of Penicillium verruculosum, is most probably derived from two L-amino acids, phenylalanine and pipecolic acid (Macmillan et aL, 1976). 

---