Bioprocess and Algae Reactor Technology, Apoptosis

266 Pages·1997·14.99 MB·English

by  Thomas Scheper

59
Advances in Biochemical Engineering
Biotechnology
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With Contributions by
M. A1-Rubeai, J. F. Cornet, C. G. Dussap,
C. B. Elias, J. Gomes, J.-B. Gros, D. C. Hill,
J. B. Joshi, A.S. Menawat, L. J. Nisbet, O. Pulz,
K. Scheibenbogen, S. R. Wrigley
With 56 Figures and 1 Color Figure
r e g n~ i r p S
This series represents critical reviews on the present and future trends in
Biochemical Engineering/Biotechnology, including microbiology, genetics,
biochemistry, chemistry, computer science and chemical engineering. It is
addressed to all scientists at universities and in industry who wish to keep up-
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In references Advances in Biochemical Engineering/Biotechnology is
abbreviated as Adv. Biochem. Engin./Biotechnol. as a journal.
ISBN3-540-63417-7 Springer-Verlag Berlin HeidelbergNewYork
Library of Congress Catalog Card Number 72-152360
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(cid:14)9 Springer-Verlag Berlin Heidelberg 1998
ISSN 5416-4270
Printed in Germany
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Managing Editor
Professor Dr. T. Scheper
Institute of Technical Chemistry, University of Hannover
CallinstraBe 3, D - 30167 Hannover/FRG
Editorial Board
Prof. .rD .W Babel Center of Environmental Research
ellaH-gizpieL GmbH
noitceS of latnemnorivnE Microbiology
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Prof. .rD H.W. Blanch University of Califomia
Department of Chemical Engineering
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Prof. .rD .hC L. Cooney sttesuhcassaM Institute of Technology
Department of Chemical Engineering
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Prof. .rD S.-O. Enfors tnemtrapeD of Biochemistry and Biotechnology
Royal Institute of Technology
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Prof. .rD K.-E. L. Eriksson Center for Biological Resource Recovery
The University of Georgia
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Prof. .rD A. Fiechter etutitsnI of Biotechnology
Eidgen6ssische Technische Hochschule
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Prof. .rD A. M. Klibanov sttesuhcassaM Institute of Technology
Department of Chemistry
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Chemical Center, Lund University
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VI Editorial Board
Prof. Dr. H. J. Rehm Westt~lische Wilhelms-Universit~t Mtinster
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University of Hannover
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Prof. Dr. U yon Stockar Swiss Federal Institute of Technology Lausanne
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Table of Contents
Fed-Batch Bioproduction of Spectinomycin
J. Gomes, A. S. Menawat ................................ 1
Role of Hydrodynamic Shear on Activity and Structure
of Proteins
C. B. Elias, J. B. Joshi ................................... 47
Novel Screen Methodologies for Identification of New
Microbial Metabolites with Pharmacological Activity
D. C. Hill, S. K. Wrigley, L. J. Nisbet ...................... 73
Photobioreactors: Design and Performance with Respect
to Light Energy Input
O. Pulz, K. Scheibenbogen ............................... 123
Kinetics and Energetics of Photosynthetic Microorganisms
in Photobioreactors
J.-F. Cornet, C. G. Dussap, J.-B. Gros ...................... 153
Apoptosis and Cell Culture Technology
M. AI-Rubeai ............................................ 225
Author Index Volumes 51 - 59 .......................... 251
Subject Index ......................................... 255
Fed-Batch Bioproduction of Spectinomycin
J. Gomes* and A.S. Menawat**
* Department of Biochemical Engineering & Biotechnology,
Indian Institute of Technology, Delhi, Hauz Khas, New Delhi 110016, India
** Advanced Solutions & Know-how, 1426, Hidden Creek North, Saline,
MI-48176, USA
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 spectino-
mycin 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.
List of Symbols and Abbreviations .................................. 2
1 Introduction ............................................. 4
1.1 Physiology of Antibiotics ................................... 4
1.1.t Carbon Regulation .................................... 6
1.1.2 Nitrogen Regulation ................................... 6
1.1.3 Phosphate Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2 Spectinomycin Biosynthesis ..................................... 8
2.1 Organism and Metabolism .................................. 8
2.2 Role of Glucose and Oxygen ................................. 10
3 Bioproduction of Spectinomycin .................................. 12
3.1 Preparation of Inoculum .................................... 12
3.2 Bioproduction Media ...................................... 13
3.3 On-Line and Off-Line Analysis ................................ 13
3.4 Spectinomycin Estimation ................................... 15
4 Fed-Batch Cultivation ........................................ 17
4.1 Glucose Feed Optimization .................................. 17
4.2 Characteristics of Spectinomycin Bioproduction ...................... 20
4.3 Influence of Residual Glucose Concentration ........................ 21
4.4 Variations in Air Flow Rate .................................. 22
5 Two Metabolite Hypothesis .................................... 23
6 Exponential Structure for Mechanistic Model .......................... 25
6.1 Model Simulation ........................................ 26
7 Prediction ............. .................................. 31
7.1 External Differential Representation ............................. 31
7.2 Air Flow Rate .......................................... 32
7.3 Spectinomycin .......................................... 36
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