| dc.description.abstract | The realization of the tremendous importance of the metabolites of molds (filamentous fungi) by microbiologists and biochemists is of fairly recent origin. Unfortunately, the reactions which take place in these organisms present considerable complexities, resulting largely from the great diversity of chemical bodies occurring in the living cell.
A detailed study, however, indicates that the agencies responsible for these vital transformations offer a close analogy to the so?called catalysts of inorganic chemistry. Their diversity is very great: some are essential for the normal regulation of growth, while others are elaborated due to environmental conditions, adaptation, etc.
It is of fundamental interest to biochemists to investigate the metabolic course of various substrates, inorganic and organic, that support and promote the complex life cycle of molds. The present thesis is an attempt by the author to understand the nature and mechanism of certain biochemical reactions incumbent on the growth of the penicillin?producing molds Penicillium chrysogenum and Penicillium notatum, the isolation and characterization of some of the metabolites, and wherever possible, to arrive at a correlation to penicillin formation.
Part I deals with certain aspects of “Overflow Carbohydrate Metabolism,” i.e., the formation of higher oligosaccharides from simple carbohydrates. This comprises seven chapters.
A fairly exhaustive survey of literature regarding carbohydrate metabolism of molds is given in the introduction. The efficacy of Penicillium chrysogenum and Penicillium notatum to form penicillin when different carbohydrates are fed as the energy source, and the day?to?day changes in the composition of the broth filtrate, have been followed qualitatively and quantitatively. Synthesis of higher oligosaccharides from maltose is described, their chemical constitution determined, and their partial purification and kinetics of reaction during mold growth observed.
Various oligosaccharides synthesized from maltose have been isolated by column chromatography and characterized by:
(a) reducing value and products on partial hydrolysis,
(b) derivatives,
(c) physical constants,
(d) mobility on paper chromatography,
(e) comparison with hydrolysates of known polysaccharides,
(f) action of diastatic enzymes, and
(g) priming capacity on phosphorylase.
Results of periodate oxidation and chain length studies are given, and the mechanism of their formation in light of experimental data is discussed. The mold is also capable of synthesizing oligosaccharides from sucrose, which have been resolved into individual components by preparative circular paper chromatography and identified.
Studies on the kinetics of transfructosidation are presented, showing close similarity between transglucosidase and transfructosidase. The mechanism of fructose?containing oligosaccharide formation is discussed in detail, with possible correlation to penicillin biosynthesis.
Part II deals with nitrogen metabolism and comprises four chapters.
A critical survey of the literature on nitrogen metabolism of Penicillium chrysogenum and Penicillium notatum and its relation to penicillin formation is given. The formation of intermediates involved in nitrogen metabolism, such as amino acids and keto acids, has been followed qualitatively and quantitatively during mold growth in synthetic media. Changes in amino acid composition in complex corn?steep liquor medium are described in detail.
Results show the presence of transaminase and amino acid oxidase in the mold, enzymes responsible for synthesis and utilization of amino acids. The kinetics of transaminase reaction have been studied and critically discussed.
Pterygospermin, a plant antibiotic that inhibits mold growth at very low dilution, has been found to inhibit transaminase activity. The bearing of this result on the antibiotic action of pterygospermin is indicated. | |
