ABSTRACT
Actinomycetes produce about 67% of the known antibiotics covering a wide range of chemical structures. However, their filamentous growth present several problems during industrial processes. Among these problems oxygen transfer limitation is critical. In this chapter we present the role of oxygen in spectinomycin production by a Streptomyces species. Spectinomycin, a broad spectrum antibiotic effective against penicillin resistant gonorrhea, is an aminoglycoside constituted from two glucose moieties. Its bioproduction is strongly influenced by glucose and oxygen. We have shown that for a fixed dissolved oxygen concentration, there are two specific glucose concentrations which give maximum final titers of spectinomycin. The bi-modal maximum indicates the influence of two intermediate metabolites in spectinomycin biosynthesis. We propose a mechanism for spectinomycin biosynthesis and subsequently develop a model based on this mechanism. The proposed mechanism for spectinomycin biosynthesis is validated by successfully reconstructing the air flow rate profiles. A nonlinear systems theory technique termed External Differential Representation, is implemented to reconstruct the spectinomycin bioconversion process which then predicts the spectinomycin concentration from the air flow rate profile. This signifies that spectinomycin titers in industrial fed-batch processes can be controlled if a priori information about the air flow rate profile yielding maximum spectinomycin is available.
Subject(s)
Spectinomycin/biosynthesis , Streptomyces/metabolism , Glucose/metabolism , Kinetics , Methionine/metabolism , Molecular Structure , Oxygen/metabolism , Spectinomycin/chemistry , Vitamin B 12/metabolismABSTRACT
Adenosine 3':5' cyclic monophosphate seems to regulate antibiotic biosynthesis and secondary metabolism in tylosin-producing cultures of Streptomyces fradiae C373.1. A dose-dependent response is observed by exogenous additions of dibutyryl cyclic AMP (cAMP), and is related to the nutritional status of the culture. Addition of cAMP to cultures growing in nutritionally lean media caused higher cumulative antibiotic tigers and some cellular differentiation compared with the control. In nutritionally rich media, a qualitatively different behavior resulted: an almost instantaneous shift toward secondary metabolism occurred. The response is characterized by extensive cellular differentiation with little growth and only a trace of antibiotic production. The possible role of cyclic AMP n the regulation of tylosin biosynthesis and secondary metabolism and its relation to specific nutrient limitations in synthetic, defined media in Streptomyces fradiae is discussed.
Subject(s)
Ehlers-Danlos Syndrome/genetics , Adult , Ehlers-Danlos Syndrome/diagnosis , Humans , MaleSubject(s)
Porphyrias/diagnosis , Acute Disease , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , India , Infant , Infant, Newborn , Male , Middle Aged , Porphyrias/epidemiologyABSTRACT
Twenty cases of acute intermittent porphyria were studied during the acute phase. Cardiovascular manifestations were noted in all the cases, with tachycardia in 20 and with hypertension in 17. Propranolol in doses ranging from 20--200 mg was given to all the cases and produced adequate control of tachycardia and hypertension. At follow-up, smaller doses of propranolol were found to maintain the pulse rate and BP within normal limits and also to prevent acute attacks.
