Relationship between Fatty‐Acid and Phenol Synthesis in Aspergillus fumigatus

Abstract

Investigations have been conducted into the relationship between fatty acid and phenol synthesis in submerged cultures of Aspergillus fumigatus. Both groups of metabolites are derived from acetate but phenol synthesis only occurs a t a late stage in the incubation period and is dependent on a change in the internal environment of the mycelium. Secretion of acetate-derived phenols commenced many hours after exhaustion of ammonium ions from the culture medium, or transfer of mycelium to glucose solution. Lipid synthesis, however, was maintained a t this stage and continued into the phenol-secreting phase when sufficient glucose was present to provide the necessary substrates. The additional lipid formed was identified as triglyceride.The composition of fatty acids in the total lipids was very similar to that found in other , Aspergillus sp. and related Ascomycetes and consisted principally of C18:2 with c16:0, c 1 6 : 1 , C1s:o and Cmi. Addition of 4-fluorophenylalanine, but not cycloheximide, caused a rapid reduction in fatty acid synthetase activity and lipid synthesis, and abolished formation of orsellinic acid and trihydroxytoluene, the normal secreted products.Certain enzymes examined, including the dehydrogenases of the pentose phosphate pathway, maintained their specific activity during the "stationary" phase whereas fatty acid synthetase was present at greatly reduced activity. The activity of ATP citrate lyase was severely reduced to an undetectable level after approximately 40 h incubation; acetyl-CoA would therefore not be made available for fatty acid, phenol or ergosterol synthesis after this time.Initiation of phenol synthesis cannot be ascribed simply to diversion of substrates from fatty acid synthesis or to reduction in fatty acid synthetase activity.Fatty acids together with a large group of naturally-occurring phenols are formed by means of condensation reactions between acetyl-CoA and malonylCoA. The synthesis of the latter products, however, entails few if any reductive steps and the oxygen functions from the malonyl residues are therefore often retained as phenolic groups. A phenomenon that is common to the synthesis of fatty acids and phenols in fungi lies in their formation as a response to deprivation of an essentialnutrient with a resultant disturbance to the internal environment of the cell [l]. Growth of the organism then ceases and the mycelium enters a stage that resembles the stationary Abbreviation. POPOP, p-bis,2-(5-phenyloxazolyl)benTrivial Name. Ergosterol, 5,7,22-ergostatrien-3B-01. Enzymes.

Importance of stored triacylglycerols in Streptomyces: possible carbon source for antibiotics

“…This condition would allow for the conversion of excess sugar into TAG, and indicates that the nitrogen content of the medium plays an important role in its accumulation. This aspect of metabolism resembles the synthesis of TAG in certain fungi and oleaginous yeasts (Ward & Packter, 1974;Ratledge, 1976 ;Holdsworth & Ratledge, 1988) and other storage polymers such as glycogen (Preiss & Romeo, 1989) and polyhydroxybutyrate (Dawes & Senior, 1973) in bacteria. However, TAG has not been considered a storage product in prokaryotes (Lennarz, 1966 ;Shaw, 1974), but Streptomyces do differ from many other bacteria in a number of features, not least in their filamentous nature and their ability to sporulate and to produce a wide range of antibiotics.…”

Biosynthesis of wall‐linked teichuronic acid by a wall‐plus‐membrane preparation from Micrococcus luteus

“…The inhibitory actions of tunicamycin and bacitracin suggest that the lipid carrier might be a polyisoprenyl phosphate. and all other substrates were prepared as before [6,9]. Reaction mixtures contained in a final volnme of 0.2 ml: 50 mM Tris/HCl, pH 8.0,20 mM MgCla, 1 mM 2-mercaptoethanol, 100 mM NH,Cl, 15 mM ATP, 2.5 mM glycine and wall-plus-membrane preparation (0.1 ml, protein concentration 3-8 mg/ml).…”

“…Paper chromatography was in solvent A, isobutyric acid: 0.5 M ammonia (5:3 v/v). All determinations of radioactivity and analytical methods were as previously described [6,9].…”

Stimulation of leucomycin production by magnesium phosphate and its relevance to nitrogen catabolite regulation

“…Several papers have described the inhibition of the formation of antibiotics by ammonium ions and by rapidly utilized nitrogen sources (1,3,4,9,11,12,14). Although the exact biochemical basis of the inhibition is not available, the phenomenon is called nitrogen catabolite regulation by analogy with carbon catabolite regulation, in which carbon catabolites are known to inhibit antibiotic formation (2).…”

“…The time course study of the ammonia content in the presence of magnesium phosphate (Fig. 3B) revealed that (3), cephamycin (1), novobiocin (11), candihexin (4), fusidic acid (9), or trihydroxytoluene (14), was suggested to be subject to nitrogen catabolite regulation, and the production of oleandomycin, a macrolide antibiotic, was shown to be inhibited by high concentrations of ammonium ions (12), but the exact mechanism of the inhibition is not known. The production of leucomycin by S. kitasatoensis studied here was similarly inhibited in the pres- It is reasonable to suppose that the nitrogen catabolite regulation is reduced under a low ammonium ion concentration created by magnesium phosphate.…”