History Of Modern Biotechnology II - Springer.pdf - Biotechnology - annam101

Preface

The aim of the Advances of Biochemical Engineering/Biotechnology is to keep

the reader informed on the recent progress in the industrial application of

biology.Genetical engineering,metabolism ond bioprocess development includ-

ing analytics, automation and new software are the dominant fields of interest.

Thereby progress made in microbiology, plant and animal cell culture has been

reviewed for the last decade or so.

The Special Issue on the History of Biotechnology (splitted into Vol.69 and 70)

is an exception to the otherwise forward oriented editorial policy.It covers a time

span of approximately fifty years and describes the changes from a time with

rather characteristic features of empirical strategies to highly developed and

specialized enterprises. Success of the present biotechnology still depends on

substantial investment in R&D undertaken by private and public investors,

researchers, and enterpreneurs. Also a number of new scientific and business

oriented organisations aim at the promotion of science and technology and the

transfer to active enterprises, capital raising, improvement of education and

fostering international relationships. Most of these activities related to modern

biotechnology did not exist immediately after the war. Scientists worked in

small groups and an established science policy didn’t exist.

This situation explains the long period of time from the detection of the anti-

biotic effect by Alexander Fleming in 1928 to the rat and mouse testing by Brian

Chain and Howart Florey (1940).The following developments up to the produc-

tion level were a real breakthrough not only biologically (penicillin was the first

antibiotic) but also technically (first scaled-up microbial mass culture under

sterile conditions). The antibiotic industry provided the processing strategies

for strain improvement (selection of mutants) and the search for new strains

(screening) as well as the technologies for the aseptic mass culture and down-

stream processing. The process can therefore be considered as one of the major

developments of that time what gradually evolved into “Biotechnology” in the

late 1960s. Reasons for the new name were the potential application of a “new”

(molecular) biology with its “new” (molecular) genetics, the invention of elec-

tronic computing and information science. A fascinating time for all who were

interested in modern Biotechnology.

True gene technology succeeded after the first gene transfer into Escherichia

coli in 1973. About one decade of hard work and massive investments were

necessary for reaching the market place with the first recombinant product.

Since then gene transfer in microbes, animal and plant cells has become a well-

Preface

established biological technology. The number of registered drugs for example

may exceed some fifty by the year 2000.

During the last 25 years, several fundamental methods have been developed.

Gene transfer in higher plants or vertebrates and sequencing of genes and entire

genomes and even cloning of animals has become possible.

Some 15 microbes, including bakers yeast have been genetically identified.

Even very large genomes with billions of sequences such as the human genome

are being investigated. Thereby new methods of highest efficiency for sequenc-

ing, data processing, gene identification and interaction are available repre-

senting the basis of genomics – together with proteomics a new field of bio-

technology.

However, the fast developments of genomics in particular did not have just

positive effects in society. Anger and fear began. A dwindling acceptance of

“Biotechnology” in medicine, agriculture, food and pharma production has

become a political matter. New legislation has asked for restrictions in genome

modifications of vertebrates, higher plants, production of genetically modified

food, patenting of transgenic animals or sequenced parts of genomes. Also

research has become hampered by strict rules on selection of programs,

organisms,methods,technologies and on biosafety indoors and outdoors.

As a consequence process development and production processes are of a high

standard which is maintained by extended computer applications for process

control and production management. GMP procedures are now standard and

prerequisites for the registation of pharmaceuticals. Biotechnology is a safe tech-

nology with a sound biological basis,a high-tech standard,and steadily improving

efficiency.The ethical and social problems arising in agriculture and medicine are

still controversial.

The authors of the Special Issue are scientists from the early days who are

familiar with the fascinating history of modern biotechnology.They have success-

fully contributed to the development of their particular area of specialization

and have laid down the sound basis of a fast expanding knowledge. They were

confronted with the new constellation of combining biology with engineering.

These fields emerged from different backgrounds and had to adapt to new

methods and styles of collaboration.

The historical aspects of the fundamental problems of biology and engineering

depict a fascinating story of stimulation, going astray, success, delay and satis-

faction.

I would like to acknowledge the proposal of the managing editor and the

publisher for planning this kind of publication. It is his hope that the material

presented may stimulate the new generations of scientists into continuing the re-

warding promises of biotechnology after the beginning of the new millenium.

Zürich,August 2000

Armin Fiechter

The Morphology of Filamentous Fungi

N.W.F.Kossen

Park Berkenoord 15,2641CW Pijnacker,The Netherlands

E-mail: kossen.nwf@inter.nl.net

The morphology of fungi has received attention from both pure and applied scientists.The

subject is complicated,because many genes and physiological mechanisms are involved in the

development of a particular morphological type: its morphogenesis.The contribution from

pure physiologists is growing steadily as more and more details of the transport processes

and the kinetics involved in the morphogenesis become known. A short survey of these

results is presented.

Various mathematical models have been developed for the morphogenesis as such, but

also for the direct relation between morphology and productivity – as production takes place

only in a specific morphological type.The physiological basis for a number of these models

varies from thorough to rather questionable.In some models,assumptions have been made

that are in conflict with existing physiological know-how.Whether or not this is a problem

depends on the purpose of the model and on its use for extrapolation.Parameter evaluation

is another aspect that comes into play here.

The genetics behind morphogenesis is not yet very well developed,but needs to be given

full attention because present models and practices are based almost entirely on the influence

of environmental factors on morphology. This makes morphogenesis rather difficult to

control, because environmental factors vary considerably during production as well as on

scale.Genetically controlled morphogenesis might solve this problem.

Apart from a direct relation between morphology and productivity, there is an indirect

relation between them, via the influence of morphology on transport phenomena in the

bioreactor. The best way to study this relation is with viscosity as a separate contributing

factor.

Keywords. Environmental factors, Filamentous fungi, Genetics, Modelling, Morphology,

Physiology,Transport phenomena

1 General Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 3

2 The Framework of This Study . . . . . . . . . . . . . . . . . . . . . 4

3 Introduction to orphology . . . . . . . . . . . . . . . . . . . . . 5

3.1 What Is Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . 5

3.2 The Morphology of Filamentous Fungi . . . . . . . . . . . . . . . 6

4 Overview of the Research . . . . . . . . . . . . . . . . . . . . . . . 7

4.1 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4.2 Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

4.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Advances in Biochemical Engineering/

Biotechnology,Vol.70

Managing Editor: Th.Scheper

N.W.F.Kossen

4.2.1.1 Building Blocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

4.2.1.2 Transport Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . 11

4.2.1.3 Synthesis of the Cell Wall:Chitin . . . . . . . . . . . . . . . . . . . 12

4.2.1.4 Synthesis of the Cell Wall:Glucan . . . . . . . . . . . . . . . . . . . 13

4.2.1.5 Synthesis of the Cell Wall:the Structure . . . . . . . . . . . . . . . 13

4.2.2 Morphology Modelling in General . . . . . . . . . . . . . . . . . . 14

4.2.3 Models for Morphogenesis . . . . . . . . . . . . . . . . . . . . . . 15

4.2.4 Models for the Relation Between Morphology and Production . . 20

4.2.5 Some General Remarks About Models . . . . . . . . . . . . . . . . 21

4.3 Special Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

4.3.1 Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

4.3.2 Whole Broth Properties . . . . . . . . . . . . . . . . . . . . . . . . 26

5 Implementation of the Results . . . . . . . . . . . . . . . . . . . . 28

6 Conclusions and Prospects . . . . . . . . . . . . . . . . . . . . . . 29

Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

List of Symbols and Abbreviations

C Concentration,kg m –3

C X Concentration of biomass,kg m –3

DCR Diffusion with chemical reaction

ID Diffusion coefficient,m 2 s –1

DOT Dissolved oxygen tension,N m –2

D r Stirrer diameter,m

d h Diameter of hypha,m

ER Endoplasmatic reticulum (an internal structure element of a cell)

f(x,t) Population density function: number per m 3 with property x at

time t

k 1 ,k 2 Lumped parameters

k l a Mass transfer parameter,s –1

L Length of hypha,m

L e Length of main hypha in hyphal element,m

L emax Maximum length of main hypha capable of withstanding fragmenta-

tion,m

L equil Equilibrium length,m

L t Length of all hyphae in hyphal element,m

L hgu Length of hyphal growth unit (L t /n),m

m mass,kg

m hgu Mass of a hyphal growth unit,kg per tip

N Rotational speed of stirrer,s –1

n Number of tips in hyphal element,-

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