Typical Growth Curve for a

Bacterial Population
Stationary Phase
z Starts at the end of the Deceleration Phase,
when the net growth rate is zero (no cell
division, or growth rate is equal to death rate)
z Cells are still metabolically active, and can
produce secondary metabolites
• Primary metabolites are growth-related products, while
secondary metabolites are non-growth-related
• Many antibiotics and some hormones are produced as
secondary metabolites
• Secondary metabolites are produced as a result of
metabolite deregulation
Stationary Phase
z During this phase, one or more of the
following phenomena may occur:
• Total cell mass concentration may stay
constant, but the number of viable cells may
decrease
• Cell lysis may occur, and viable cell mass may
drop. A second growth phase may occur as
cells grow on lysis products from the dead cells
(cryptic growth)
• Cells may not be growing, but may have active
metabolism to produce secondary metabolites
Stationary Phase
z During the stationary phase, the cell
catabolizes cellular reserves for new building
blocks and for energy-producing monomers
• This is called endogenous metabolism
z The cell must expend maintenance energy in
order to stay alive
• The equation that describes the conversion of cellular
mass into energy, or the loss of cell mass due to lysis
during the stationary phase is:
dX
= −k d X or X = X S 0e − kd t (6.9)
dt
Death Phase
z The death or decline phase is characterized by
the expression:
dN − k d' t
= −k d N or N = N s e
'
(6.10)
dt
z Where Ns is the concentration of cells at the
end of the stationary phase, and k d' is the first-
order death-rate constant
z A plot of ln N versus t yields a line of slope − k '
d
Yield Coefficients
z Growth kinetics are generally further
described by defining stoichiometrically
related parameters
z Yield coefficients are defined based on the
amount of consumption of a given material
• For example, the growth yield coefficient is:
∆X
YX S = − (6.11)
∆S
• For organisms growing aerobically on glucose, YX/S
is typically 0.4 to 0.6 g/g, for most yeast and
bacteria; anaerobic growth is much less efficient
Aerobic and Anerobic Growth
Yields of S. faecalis on Glucose
Yield Coefficients
z At the end of a batch growth period, there is an
apparent or observed growth yield (eq. 6.12):

∆S = ∆Sassimilation + ∆Sassimilation + ∆Sgrowth + ∆Smaintenance

into biomass into an energy energy
extracellular
product

z The apparent yield is not a true constant for

compounds that can be used as both a carbon
and energy source, but the true growth yield
(YX/S) is constant
Yield Coefficients
z Yield coefficients can also be defined for other
substrates or for product formation:
∆X
YX O2 =− (6.13)
∆O2

∆P
YP S =− (6.14)
∆S
z YX/O is typically 0.9 to 1.4 g/g for most yeast
2
and bacteria, but is much lower for highly
reduced substrates (e.g. methane, CH4)
Summary of Yield Factors for
Aerobic Growth
The Maintenance Coefficient
z The maintenance coefficient is used to describe the
specific rate of substrate uptake for cellular
maintenance:
m≡−
[dS dt ]m (6.15)
X
z However, during the Stationary Phase, where little
external substrate is available, endogenous metabolism
of biomass components is used for maintenance energy
z Maintenance energy is the energy required to repair
damaged cellular components, to transfer nutrients and
products in and out of cells, for motility, and to adjust
the osmolarity of the cells’ interior volume
Microbial Products
z Microbial products can be classified into
three major categories
z Growth-associated products
• These products are produced simultaneously
with microbial growth
• Specific rate of product formation is
proportional to the specific growth rate, µg
• Note that µg is not equal to µnet, the net
specific growth rate, when endogenous
metabolism is occurring
Growth-Associated Products
z The rate expression for product formation in
growth-associated production is:
1 dP
qp = = YP X µ g (6.16)
X dt
z Where qp is the rate of product formation (h-1)
z The production of a constitutive (continuously
produced, as opposed to inducible) enzyme
is an example of a growth-associated product
Non-Growth-Associated Products
z Non-growth-associated product formation
takes place during the Stationary Phase,
when the growth rate is zero
z Specific rate of product formation is constant:
q p = β = constant (6.17)

z Many secondary metabolites, such as most

antibiotics (e.g. penicillin), are non-growth-
associated products
Mixed-Growth-Associated Products
z Mixed-growth-associated product formation
takes place during the Deceleration (slow
growth) and Stationary Phases
z The specific rate of product formation is given
by the Luedeking-Piret equation:
q p = αµ g + β (6.18)
z If α = 0, the product is completely non-growth
associated; If β = 0, the product is completely
growth-associated
z Examples: lactic acid fermentation, production
of xanthan gum, some secondary metabolites
Kinetic Patterns of Growth and
Product Formation in Batch Culture

a) Growth-associated product formation

b) Mixed-growth-associated product formation
c) Non-growth-associated product formation
Example 6.1
Example 6.1
 X 
z From equation 6.6  ln = µ net t  ,
 X0 
z We can generate an expression of the form y=ax+b:
ln X = µ net t + ln X 0
4.5
4
Plotting ln X 3.5
3
vs t produces 2.5
ln X

a straight line 2
1.5
of slope µnet : 1
0.5
0
0 10 20 30 40
Time, t
Example 6.1