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Identification of coprogen B and its breakdown products from Histoplasma capsulatum
Abstract:
Iron added to a chemically defined liquid medium suppressed hydroxamic acid production at 37 degrees C by yeast cells of Histoplasma capsulatum. Four hydroxamic acids, HA-I, HA-II, HA-III, and HA-IV, present in the low-iron fluid after the culture of H. capsulatum were isolated by extraction and cation-exchange chromatography through cellulose phosphate (0.35% formic acid). Visible spectra of prepared ferrihydroxamates indicated that HA-II and HA-III were monohydroxamates, whereas HA-I and HA-IV were identified as di- and trihydroxamates, respectively. Reductive hydrolysis of HA-I (the major hydroxamic acid isolated) yielded ornithine. Hydrolysis of HA-IV in water or in 0.1 N NaOH resulted in the formation of HA-I (dihydroxamic acid) and HA-II (monohydroxamic acid). Based on their charge at pH 5.2 and 2 determined by paper electrophoresis, Rf values on thin-layer chromatography, infrared spectra, and reactivity to ninhydrin, three of the isolated hydroxamic acids were identified as deferricoprogen B (HA-IV) and its breakdown products, dimerumic acid (HA-I) and trans fusarinine (HA-II). HA-I and HA-IV exhibited growth factor activity for both yeast and mycelial forms of growth of H. capsulatum.
Insights
Iron suppresses hydroxamic acid production in Histoplasma capsulatum. Four hydroxamic acids were isolated and identified, with two exhibiting growth factor activity for both yeast and mycelial forms.
Area of Science:
- Mycology
- Biochemistry
- Organic Chemistry
Background:
- Histoplasma capsulatum produces hydroxamic acids.
- Iron availability influences microbial metabolism and secondary metabolite production.
- Hydroxamic acids are important iron chelators in biological systems.
Purpose of the Study:
- To investigate the effect of iron on hydroxamic acid production by Histoplasma capsulatum.
- To isolate and characterize hydroxamic acids produced by H. capsulatum.
- To determine the biological activity of isolated hydroxamic acids.
Main Methods:
- Yeast culture in a chemically defined medium with and without iron.
- Extraction and cation-exchange chromatography for hydroxamic acid isolation.
- Spectroscopic analysis (visible, infrared), reductive hydrolysis, paper electrophoresis, and thin-layer chromatography for structural identification.
Main Results:
- Iron addition significantly suppressed hydroxamic acid production.
- Four hydroxamic acids (HA-I, HA-II, HA-III, HA-IV) were isolated and characterized.
- HA-I, HA-II, and HA-IV were identified as dimerumic acid, trans fusarinine, and deferricoprogen B, respectively.
- HA-I and HA-IV demonstrated growth factor activity for both yeast and mycelial forms of H. capsulatum.
Conclusions:
- Iron regulation of hydroxamic acid synthesis in H. capsulatum was demonstrated.
- Deferricoprogen B and its derivatives are produced by H. capsulatum.
- Specific hydroxamic acids play a role in the growth and development of H. capsulatum.