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Transcript
IMMUNITY
= Ability of organism to resist infection --- by means of
interactions of a variety of cells and cell products
1. Nonspecific (innate):
Phagocytes: (1) engulf, (2) digest and (3) destroy
bacteria in lysosomes, (4) present antigens and
(5) attract cells of Specific immunity
2. Specific (adaptive)
APC=Antigen Presenting Cell
(1) Cell-mediated:
Cell
TC
degranulation
apoptosis
APC
TH1
cytokines
inflamation
(2) Humoral (antigen-antibody mediated)
APC
TH2
interleukins
Bplasma
Ig
memory cells
• The innate immune response is mediated
by phagocytes.
• Phagocytes recognize pathogen-associated
molecular patterns (PAMPs) via a family of
membrane-bound pattern-recognition
molecules, or PRMs.
•Interaction of the PAMPs with PRMs
activates phagocytes to produce metabolic
products that kill the pathogen or limit its
effects.
• Many pathogens have developed
mechanisms to inhibit phagocytes.
Phagocyte armor
1. Enzymes:
Lysozyme
Protease
Phosphatase
Lipase
Nuclease
2. Bactericides:
H-peroxide
Superoxide
Hydroxyl radical
Singlet oxygen
3. Aerobic/Anaerobic switch
4. APC – system (antigen-presenting cells)
• Nonspecific phagocytes present antigen to
Specific T cells, triggering the production of
effector T cells and antibodies.
• Immune T cells and antibodies react directly or
indirectly to neutralize or destroy the antigen.
Inflammation
is characterized by pain, swelling (edema),
redness (erythema), and heat. The inflammatory
response is a normal and generally desirable
outcome of an immune response. Uncontrolled
systemic inflammation, called septic shock, can
lead to serious illness and death.
• The adaptive immune response is
characterized by specificity for the antigen,
• The ability to respond more vigorously
when re-exposed to the same antigen i.e.
memory, and
• The ability to discriminate self antigens
from nonself antigens, i.e. tolerance.
•Specificity
•Memory
•Tolerance
• Immunogens are foreign macromolecules that
induce an immune response. Molecular size,
complexity, and physical form are intrinsic
properties of immunogens. When foreign
immunogens are introduced into a host in an
appropriate dose and route, they initiate an immune
response.
• Antigens are molecules recognized by
antibodies or T-Cell-Receptors or TCRs. Antibodies
recognize conformational determinants; TCRs
recognize linear peptide determinants.
T cells recognize antigens presented by
APCs or by pathogen-infected cells. At the
molecular level, TCRs bind peptide antigens
presented by MHC proteins. These molecular
interactions stimulate T cells to kill antigenbearing cells or to produce cell-stimulating
proteins known as cytokines.
IMMUNITY
1. Nonspecific:
phagocytosis & destruction in lysosomes
PMN, Monocytes (circulate)
Macrophages (fixed to tissue)
2. Specific
a) Cell-mediated:
Cell
TC
degranulation
apoptosis
APC
TH1
cytokines
inflamation
b) Humoral (antigen-antibody mediated)
APC
TH2
interleukins
Bplasma
Ig
memory
c) APC cells are Macrophages, Dendritic cells, B-cell
TH1 and TH2
cells play pivotal roles in cell-mediated and
antibody- mediated immune responses. TH1
inflammatory and TH2 helper cells each
stimulate effector cells through the action of
cytokines.
• T-cytotoxic (TC )cells recognize antigens on
virus-infected host cells and tumor cells
through antigen-specific TCRs.
• Antigen-specific recognition triggers killing
via perforin and granzymes.
• Natural killer (NK) cells use the same
effectors to kill virus-infected cells and
tumors. However, NK cells do not require
stimulation, nor do they exhibit memory.
NK cells respond in the absence of MHC
proteins.
Ig (antibody) proteins consist of four chains, two
heavy and two light. The antigen-binding site is
formed by the interaction of variable regions of
heavy and light chains. Each class of Ig has
different structural and functional characteristics.
Opsonization
The complement system catalyzes bacterial
cell destruction and opsonization. Complement
is triggered by antibody interactions or by
interactions with nonspecific activators.
Complement is a critical component of both
innate and adaptive host defense.
The antigen-binding site of an Ig is
composed of the V (variable) domains of one
heavy chain and one light chain. Each heavy
and light chain contains three
complementarity-determining regions, or
CDRs, that are folded together to form the
antigen-binding site.
Recombination allows shuffling of various
pieces of the final Ig genes. Random
reassortment of the heavy- and light-chain
genes maximizes genetically encoded
diversity. Imprecise joining of VDJ and VJ
segments as well as hypermutation and
affinity maturation also contribute to virtually
unlimited immunoglobulin diversity.
• Antibody production is initiated by antigen
contact with an antigen-specific B cell that
processes the antigen and presents it to
an antigen-specific TH2 cell.
• The activated TH2 cell then signals the
antigen-specific B cell to produce antibody.
• Activated B cells live for years as memory
cells and can rapidly produce large
quantities (high titers) of antibodies upon
re-exposure to antigen.
• The thymus is a primary lymphoid organ
that provides an environment for the
maturation of antigen-reactive T cells.
• Immature T cells that do not interact with
MHC protein (positive selection) or react
strongly with self antigens (negative
selection) are eliminated by clonal deletion
in the thymus.
•
T cells that survive positive and
negative selection leave the thymus
and can participate in an effective
immune response.
• B cell reactivity to self antigens is
controlled through clonal deletion,
selection, and anergy.
• Cytokines are soluble mediators produced by
leukocytes that regulate interactions between
cells. Several cytokines such as IL-1, IL-2, and
IL-4 affect leukocytes and are critical
components in the generation of specific
immune responses. Other cytokines such as
IFN and TNF affect a wide variety of cell types.
Chemokines are produced by a variety of cell
types in response to injury and are potent
attractants for nonspecific inflammatory cells
and T cells. (IL stands for Interleukin)
Cytokines – small soluble regulatory proteins
Lymphokines – cytokines produced by lymphocytes
Interleukins – interleucocyte regulation
IL1
IL2
IL3
IL4
IL5
IL8
IL10
IL12
Macrophages to TH  activation
TH2 to TH2  autocrene proliferation
TH1 to stem cells
TH2 to B  proliferation plasma cells IgG, E
TH2 to B  proliferation plasma cells lgA
Leukocytes chemoattracts T-cells & PMNs
TH2 to TH1  inhibition
Macrophages to TH1  activation
Chemokines
IFN – InterFeroNs leukocytes  tissue cells – antiviral
TGF – T-cell Growth Factor
TNF – Tumor Necrosis Factor
MCP – Macrophage Chemoattractant Protein
Immunization
Agammaglobulinemia
Exposure
Receives immunogens
Active: Immunogens
Natural
Artificial
Immunization
(vaccination)
Active
Passive
Receives antibodies
Passive: antiserum (antitoxin)
Killed pathogens (formaldehyde) Antibodies in serum
Attenuated strains of pathogens Hyperimmune persons
Toxoids
Pooled Immunoglobulins
1. Synthetic epitope peptide;
2. Recombinant vector vaccine: Viral genes cloned in E. coli
3. Cloned genes injected and expressed (tumor-specific antigen)
Hypersensitivity - type I
Immediate hypersensitivity
Allergy, asthma, anaphylaxis
Hypersensitivity - type II
Organ-specific Autoimmune diseases
Autoantibodies:
Hashimoto’s disease against thyroid gland
Juvenile diabetes against Langerhans islets
Hypersensitivity - type III
Systemic Autoimmune diseases
Systemic lupus erythematosis (SLE)
Hypersensitivity - type IV
Delayed hypersensitivity
Contact dermatitis, tuberculin test
• Immunity to infectious disease can be either
passive or active, natural or artificial.
• Immunization, a form of artificial active
immunity, is widely employed to prevent infectious
diseases.
• Most agents used for immunization are either
attenuated or inactivated pathogens or inactivated
forms of natural microbial products.
Hypersensitivity results when foreign antigens
induce cellular or antibody immune responses,
leading to host tissue damage. Autoimmunity
occurs when the immune response is directed
against self-antigens, resulting in host tissue
damage.
Hypersensitivity - type I
Immediate hypersensitivity
Allergy, asthma, anaphylaxis
Hypersensitivity - type II
Organ-specific Autoimmune diseases
Autoantibodies:
Hashimoto’s disease against thyroid gland
Juvenile diabetes against Langerhans islets
Hypersensitivity - type III
Systemic Autoimmune diseases
Systemic lupus erythematosis (SLE)
Hypersensitivity - type IV
Delayed hypersensitivity
Contact dermatitis, tuberculin test
T-cell
Cytotoxic Attack
B-cell
Antibody Attack
T-cell
Complement
alternatives
Mimicry
(Rabies,
Rhino,
Vaccinia)
Hiding the binding site
(Polyo, Influenza, HIV)
Epitope cover-up (wolf in sheep’s skin – E. coli)
Hiding
in the police
Department
(Shigella,
Mycobacterium,
Chlamydia)
Clinical methods
- Culture diagnostic:
- Blood , Bacteremia -> Septicemia -> Septic shock
- Urine , Bacteriuria – bacteria in urin
- Feces, Salmonella, Shigella
- Antibiogram
- Serodiagnostic
- Antibody titer
- Polyclonal antibodies
- Monoclonal antibodies
Safety in the clinical laboratory requires effective
training, planning, and care to prevent the infection
of laboratory workers with pathogens. Materials
such as live cultures, inoculated culture media,
used hypodermic needles, and patient specimens
require specific precautions for safe handling.
Proper sampling and culture of the suspected
pathogen is the most reliable way to identify an organism
that causes a disease. The selection of appropriate
sampling and culture conditions requires knowledge of
bacterial ecology, physiology, and nutrition.
Antimicrobial drugs are widely used for the
treatment of infectious diseases. Pathogens should
be tested for susceptibility to individual antibiotics
to ensure appropriate chemotherapy. This rigorous
approach to antimicrobial drug treatment is usually
applied only in health care settings.
An immune response is a natural outcome of
infection. Specific immune responses,
particularly antibody titers and skin tests, can
be monitored to provide information
concerning past infections, current infections,
and convalescence.
Polyclonal and Monoclonal antibodies
are used for research and clinical
applications. Hybridoma technology provides
reproducible, monospecific antibodies for a
wide range of clinical, diagnostic, and
research purposes.
Antigen–antibody reactions require that
antibody bind to antigen. Specificity and sensitivity
define the accuracy of individual serological tests.
Neutralization and precipitation reactions are
examples of antigen-binding tests that produce
visible results involving antigen–antibody
interactions.
• In serological reactions, high specificity
prevents false-positive reactions. High
sensitivity prevents false-negative
reactions.
Specificity: binding with a single antigen
(positive + negative controls no false +)
Sensitivity: lowest amount of antigen dedectable
(no false -)
______________________________________
Precipitation
soluble - soluble
Agglutination (100 x precipitation sensitive)
surface bound - soluble
Direct agglutination tests are widely used
for determination of blood types. A number of
passive agglutination tests are available for
identification of a variety of pathogens and
pathogen-related products. Agglutination
tests are rapid, relatively sensitive, highly
specific, simple to perform, and inexpensive.
Fluorescent antibodies are used for quick,
accurate identification of pathogens and other
antigenic substances in tissue samples and
other complex environments. Fluorescent
antibody-based methods can be used for
identification, quantitative enumeration, and
sorting of a variety of cell types.
EIA (ELISA) and RIA methods are the most
sensitive immunoassay techniques. Both
involve linking a detection system, either an
enzyme or a radioactive molecule, to an
antibody or antigen, significantly enhancing
sensitivity. ELISA and RIA are used for
clinical and research work; tests have been
designed to detect either antibody or antigen
in many applications. For more specificity
apply IMMUNOBLOT
Immunoblot procedures are used to detect
antibodies to specific antigens or to detect the
presence of the antigens themselves. The
antigens are separated by electrophoresis,
transferred (blotted) to a membrane, and
exposed to antibody. Immune complexes are
visualized with enzyme-labeled or radioactive
secondary antibodies. Immunoblots are
extremely specific, but procedures are
complex and time-consuming.
Nucleic acid hybridization is a powerful
laboratory tool used for identification of
microorganisms. A nucleic acid sequence
specific for the microorganism of interest
must be available in order to design a probe.
Perhaps the most widespread use of probebased technology is in the application of gene
amplification (PCR) methods. Various DNAbased methodologies are currently used in
clinical, food, and research laboratories.
Virus propagation in vitro can be
accomplished only in tissue culture.
Therefore, most diagnostic techniques for
viral identification are not growth-dependent,
but routinely rely on immunoassays and
nucleic acid-based techniques. Electron
microscopy techniques are useful for direct
observation of viruses in host samples.
Epidemiology
The study of disease in populations. To understand
infectious disease, the epidemiologist studies the
interactions of the pathogen with the host
population. It is a population level ecology
Concepts of Epidemiology
Prevalence: % of diseased
Incidence: # of diseased
Endemic - Epidemic - Pandemic
Mortality - Morbidity
Infection – Incubation - Acute period – Decline - Convalescence
Emerging Infectious Diseases
Transmissions:
• Reservoirs - Vectors - Carriers
Public Health Measures
• Surveillance - Reservoir control Transmission control • Immunization - Quarantine - Pathogen
eradication
Reservoires
To understand how diseases spread,
the pathogen reservoir must be known.
Some pathogens exist in soil, water, or
animals. Other pathogens exist only in
humans and are maintained solely by
person-to-person contact. An understanding
of disease carriers and pathogen life cycles
is critical for controlling disease.
• An endemic disease is constantly present at low
incidence in a specific population.
• In epidemics, an unusually high incidence of
disease occurs in a specific population.
• A pandemic disease is global
Infectious diseases cause morbidity (illness) and
may cause mortality (death). An infectious disease
follows a predictable clinical pattern in the host and
its population.
Transmission
A pathogen can be transmitted from ….
• host-to-host, … directly or
indirectly by:
• vectors …... live intermediates, or
• fomites … ..Inanimate objects
• vehicles ….use of food and water.
Epidemics origin: may be
(A) common-source or
(B) host-to-host
Common source
waterborn
Host-to-host
1. Airborn
2. Direct contact
3. Vectors - animals
Mosquito – transferred deseases
•
•
•
•
•
Malaria
Eastern equine encephalitis
Western equine encephalitis
St. Louis encephalitis
West Nile virus
Water-transmitted diseases
Salmonella typhi
Vibrio cholerae
Escherichia coli
Legionella pneumophila
Entamoeba histolithica, Giardia
Water treatment
1. Primary
2. Secondary
3. Tertiary
Parasite – Host
Co-Evolution
• Hosts and pathogens co-evolve with time and
arrive at a steady state that favors the continued
survival of both.
• With Herd immunity, a large fraction of a
population is immune to a given disease, and it is
difficult for the disease to spread.
• Disease cycles occur when a large, recurring,
non-immune population such as children entering
school is exposed to a pathogen.
Many Respiratory Pathogens are
gram-positive Bacteria. Because grampositive Bacteria are resistant to drying, they
are easily transmitted in air. Most
respiratory pathogens are transferred from
person to person via respiratory tract.
Transfer is generated by coughing,
sneezing, talking, or simply breathing.
1. Air-born transmissions – Respiratory diseases
Bacterial
1.
2.
3.
4.
5.
Streptococcus pyogenes, S. pneumoniae
Corynebacterium diphtheriae
Bordetella pertussis
Mycobacterium tuberculosis, M. leprae, M. bovis
Neisseria meningitidis
Viral
1. Measles, Mumps, Rubella, Varicella,
2. Common cold, Influenza
Diseases caused by streptococci include streptococcal
sore throat and pneumococcal pneumonia.
Occasionally, Streptococcus pyogenes infections
develop from pharyngitis into serious conditions such
as scarlet fever and rheumatic fever. Pneumonia
caused by Streptococcus pneumoniae is a serious
disease with high mortality. Definitive diagnosis for
both pathogens is by culture. Infections with both
pathogens are treatable with antimicrobial drugs,
but drug-resistant strains are known, especially for
Streptococcus pneumoniae
Tuberculosis is one of the most prevalent
and dangerous single diseases in the world.
Its incidence is on the increase in developed
countries, in part because of the emergence
of drug-resistant strains. The pathology of
tuberculosis and leprosy is influenced by the
cellular immune response.
Colds and influenza, or flu, are the most common
infectious diseases. While they are not usually lifethreatening diseases by themselves, they can
lower resistance and allow serious secondary
bacterial infections. Influenza outbreaks occur
annually and more serious epidemics and
pandemics occur periodically.
Neisseria meningitidis is a common cause of
meningococcemia and meningitis in young adults
and occasionally occurs in epidemics in closed
populations. Bacterial meningitis and
meningococcemia are serious diseases with very
high mortality rates. Treatment and prevention
strategies are in place to deal with epidemic
outbreaks, but an effective universal vaccine is not
yet available.
Infection with a novel zoonotic virus, SARS-CoV
(ssRNA), causes severe acute respiratory
syndrome (SARS). Person-to-person spread is by
respiratory means. Control of this high mortality
virus is through rapid diagnosis and isolation of
victims (source: civets, food-grown in Guandong
Province, China – Nov. 2002).
2. Direct Contact Transmission –
Sexual transmission
Bacterial
1.
2.
3.
4.
5.
6.
Staphylococcus epidermis, S. aureus – toxic shock
Helicobacter pylori
Neisseria gonorrhoeae
N. meningitidis
Treponema pallidum
Chlamydia trachomatis
Viral
1. Hepatitis A-G,
2. Herpes simplex – 1, 2,
3. HIV
Gonorrhea and syphilis, caused by Neisseria
gonorrhoeae and Treponema pallidum,
respectively, are STIs with potential serious
consequences if not treated. Although the
incidence of these diseases has generally declined
in recent years, there are still over 350,000 cases
of gonorrhea and 6000 cases of syphilis annually in
the United States.
Helicobacter pylori infection appears to be the
most common cause of gastric ulcers. Treatment of
gastric ulcers now involves antibiotics, which seem
to promote a permanent cure.
Hepatitis caused by viruses can cause cirrhosis,
an acute liver disease. HBV and HCV can cause
chronic infections leading to liver cancer. Vaccines
are available for HAV and HBV.
• The overall prevalence of hepatitis has
decreased significantly in the last 20 years in the
United States, but viral hepatitis is still a major
public health problem because of the high
infectivity of the viruses.
• Postexposure treatment: γ-globulin, HBV-specific
HIV
AIDS
Opportunistic diseases
AIDS is now one of the most prevalent infectious
diseases in the human population. HIV destroys the
immune system, and opportunistic pathogens then
kill the host. There is still no effective vaccine for
HIV. However, several antiviral drugs slow the
progress of AIDS. The only prevention for the
spread of HIV infection is through avoidance of
behavior such as intravenous drug use (needle
sharing) and unsafe sexual practices.
Nosocomial infections Many common
microorganisms have the potential to be pathogens
in a hospital environment. Hospital patients are
unusually susceptible to infectious disease and are
exposed to a variety of infectious agents, including
opportunistic pathogens, in the hospital environment.
Treatment of these infections is complicated by
antibiotic resistance.
Food and water purity regulations, vector
control, immunization, quarantine, disease
surveillance, and pathogen eradication are public
health measures that play a major role in reduction
of disease incidence.
Infectious diseases account for nearly 30% of all
worldwide mortality. Most infectious diseases occur
in developing countries. Travelers to endemic
disease areas should be immunized when possible
and should take appropriate precautions to prevent
infection.
Bacillus anthracis has emerged as an
important pathogen because of its use as a
bioweapon. Highly infective weaponized endospore
preparations have been used as bioterror agents.
Inhalation anthrax has a fatality rate of about 90%
in untreated individuals. Effective treatment relies
on timely observation and diagnosis of symptoms.
Treatment does not guarantee survival for
inhalation anthrax.
Changes in host, vector, or pathogen conditions,
whether natural or artificial, can result in conditions
that encourage the explosive emergence or
reemergence of certain infectious diseases. Global
surveillance and intervention programs must be
developed to prevent new epidemics and
pandemics.
Concepts of Epidemiology
Prevalence: % of diseased
Incidence: # of diseased
Endemic - Epidemic - Pandemic
Mortality - Morbidity
Infection-Incubation-Acute period-Decline-Convalescence
Transmissions:
Reservoirs - Vectors - Carriers
Public Health Measures
Surveillance - Reservoir control - Transmission control Immunization - Quarantine - Pathogen eradication
Emerging Infectious Diseases
Biological Weapons
INDUSTRIAL MICROOGANISMS AND
PRODUCTS
Industrial Microorganisms and Their Products
Properties of a Useful Industrial Microorganism
Examples of Industrial Products
Primary and Secondary Metabolites
Primary and Secondary Metabolism Pathways
Characteristics of Large-Scale Fermentations
Construction of an Aerobic Fermentor
Fermentation Control and Monitoring
Fermentation Scale-Up
The Scale-Up Process
• An industrial microorganism must produce
the product of interest in high yield, grow
rapidly on inexpensive culture media
available in bulk quantities, be amenable to
genetic manipulation, and, if possible, be
nonpathogenic.
• Industrial products are many and include
both cells and substances made by cells.
• Primary and secondary metabolites are
produced during active cell growth or near the
onset of stationary phase, respectively.
• Many economically valuable microbial
products are secondary metabolites.
Large-scale industrial fermentations present
several engineering problems:
• Fermentation Scale-Up
• Aerobic processes require mechanisms for
stirring and aeration.
• The microbial process must be
continuously monitored to ensure satisfactory
yields of the desired product.
Scale-up process is:
• Gradually converting a useful industrial
fermentation from laboratory scale to
• Production scale.
• Aeration is a particularly critical aspect to
monitor during scale-up studies.
MAJOR INDUSTRIAL PRODUCTS FOR THE
FOOD AND BEVERAGE INDUSTRIES
Alcohol and Alcoholic Beverages
Wine Varieties and Production
Brewing: Making the Wort
Brewing: The Fermentation Process
Distilled Alcoholic Beverages
Commodity Ethanol
MAJOR INDUSTRIAL PRODUCTS FOR THE
HEALTH INDUSTRY
Antibiotics: Isolation and Characterization
New Antibiotics, Purification, Incresed Yield
Industrial Production: Penicillins and Tetracyclines
b-Lactam Antibiotics: Penicillin and Its Relatives
Production of Tetracyclines
Vitamins and Amino Acids
Vitamins
Amino Acids
•
Beer
• Ale
• Porter
• Stout
Brewing: Making the Wort
1. Mashed grains of barley (wheat, rice, corn): Malt
2. Boiling: Natural enzymes convert starch to sugar,
protein coagulates and is removed
3. Aqueous extract removed by filtering: Wort
4. Hops is added boiled for several hours
Brewing: Making the Wort
1. Mashed grains of barley (wheat, rice, corn): Malt
2. Boiling: Natural enzymes convert starch to sugar,
protein coagulates and is removed
3. Aqueous extract removed by filtering: Wort
4. Hops is added boiled for several hours
5. Wort is sterilized, filtered, cooled & transferred to
6. Fermentation vessels
Brewing:
The Fermentation Process
Top fermenting (obergaering):
Ales, Stout, English style, (Altbier)
Sacharomyces cerevisiae
14 - 23°C ; 5 – 7 days – stored at 4-8°C
Bottom fermenting (untergaerig):
Lager (Pilsener, Pils, Spezial, Bavarian lager),
Sacharomyces carlsbergensis
6 - 12°C ; 8 -14 days – stored weeks at -1°C
•
•
•
•
•
American light beer:
Munich beer:
Oktoberfest beer
Maibock beer
Belgian beer
Wart
?
12%
>12%
>12%
?
Alcohol
3.50%
4.25%
5.00%
5.00%
?
• Alcoholic beverages are produced by yeast
from the fermentation of sugar to ethyl
alcohol and CO2.
• Wine is produced from grape juice,
• Beer from malted grain, and
• Distilled spirits from the distillation of
fermented solutions.
• Commodity alcohol is used as a gasoline
additive and industrial solvent.
Vinegar Production
Vinegar Production
Citric Acid
Citric Acid Production: The Link to Iron
Citric Acid Production: Growth Media, Conditions, and
Purification
Yeast as a Food and Food Supplement
Yeast Cell Production
Mushrooms as a Food Source
Commercial Growth of Mushrooms
The industrial production of antibiotics begins
with screening for antibiotic producers. Once
new producers are identified, purification and
chemical analyses of the antimicrobial agent
are performed. If the new antibiotic is
biologically active in vivo, the industrial
microbiologist may genetically modify the
producing strain to increase yields to levels
acceptable for commercial development.
• Major antibiotics of clinical significance
include the β-lactam antibiotics penicillin and
cephalosporin and the tetracyclines.
• All of these antibiotics are typical secondary
metabolites, and their industrial production is
well worked out . . .
• despite the fact that the biochemistry and
genetics of their biosynthesis are only
partially understood.
Vitamins produced microbially include vitamin
B12 and riboflavin, whereas the most important
amino acids produced commercially are
glutamic acid, aspartic acid, phenylalanine,
and lysine. High yields of amino acids are
obtained by modifying regulatory signals that
control synthesis of the particular amino acid
such that overproduction occurs.
Microbial biotransformation employs
microorganisms to biocatalyze a specific step
or steps in an otherwise strictly chemical
synthesis.
Microorganisms are ideal for the large-scale
production of enzymes. Many enzymes are
used in the laundry industry to remove stains
from clothing, and thermostable and
alkalistable enzymes have many advantages
in these markets. Enzymes from
extremophiles are desirable for biocatalyses
under extreme conditions. When an enzyme
is used in a large-scale process, it may be
desirable to immobilize it by bonding it to an
inert substrate.
The active ingredient in vinegar is acetic acid,
which is produced by acetic acid bacteria
oxidizing an alcohol-containing fruit juice.
Adequate aeration is the most important
consideration in ensuring a successful
vinegar process.
A number of organic chemicals are produced
commercially by use of microorganisms, of
which the most important economically is
citric acid, produced by Aspergillus niger.
Yeast cells are grown for use in the baking
and food industries. Commercial yeast is
produced in large-scale aerated fermentors
using molasses as the main carbon and
energy source.