The optimal allocation of building blocks between nutrient

uptake systems in a microbe and the optimal allocation between nutrient uptake and growth in a microbial trichome
by Richard John Gibson
The papers on which this essay is based are the optimal allocation of building blocks between nutrient
uptake systems in a microbe, by van den Berg et al [1], and the optimal allocation between nutrient uptake
and growth in a microbial trichome, by van den Berg et al [2]. The main questions addressed by the papers are
how a microbe can best allocate its resources into the creation of assimilatory and proliferative machinery and
the optimal allocation for growth of assimilatory machinery to the uptake of different nutrients.
The first question is answered by a derivation of an optimal allocation regime formulated from a twodimensional non-linear optimal control problem for the Droop quota model and the second question by the
development of a mathematical model with a feedback method as described in [3]. Past results were discussed
in both papers, with further modifications to the model suggested and the physiological significance being
discussed.

Nutrient uptake and growth in microbes

Microorganisms (microbes) are microscopic organisms that include a very diverse range of organisms, including
bacteria, archaea, many types of fungi, protozoa and algae. Viruses are also sometimes classes as microbes,
although this is highly contencious due to the debate about whether viruses are living [4]. Microbes can be both
uni and multicellular [5] and live in all parts of the biosphere and understanding more about them is vital to
biotechnologies, such as genetic engineering and bioinformatics [6].
The primary focus of a microbe, as with any living organism, is to reproduce. It is therefore imperative that
the microbe utilises the available resources in a way that allows it to grow. Unlike multicellular forms of life
that have evolved to be comprised of specialised structures that are able to create a stable environment for their
cells, microbes are able to exert little control over their environment due to their unicellular form. Almost all
envirornments undergo fluctuations in conditions, be it pH levels, the amount of organic nutrients present, or
temperature. As a result, microbes face a struggle to reproduce and must become extremely efficient in their
utilisation of resources available in the environment to have any realistic chance of survival. Microbes must
take up the optimal amounts of each nutrients for the wellbeing of the cell and use them in an efficient way. As
extanct microbes have survived and evolved over an extremely long time period they have became efficient in
the uptake and allocation of available resources. Therefore, understanding more about their allocation regimes

could lead to a wealth of utilisable information that could be used to optimise other processes. However, if
microbes are able to procreate enough to be in large numbers then spatial and temporal fluctuations may be
minimised due to lower energy fluxes occuring [7].
Microbes use nutrients to synthesize building blocks through biosynthetic pathways consisting of several
hundred enzyme-catalysed reactions. Biosynthetic reactions in microbes have an extraordinary metabolic
diversity that allow them to metabolise almost any organic compound. This process has been observed to
create amino acids, nucleotides, sugars, fatty acids and coenzymes. Microbes devote a certain percentage
of their amino acid building blocks into making proteins, known as transporters. Transporters are involved
in the assimilation of nutrients (such as light and minerals) from the ambient environment. There are four
ways that nutrients may enter a microbe: simple diffusion, facilitated diffusion, active transport, and group
translocation. Simple diffusion happens in the case of molecules such as O2 , H2 O and CO2 , where they diffuse
through the membrane of the microbe. Diffusion can also be facilitated by transmembrane proteins, known
as stereospecific proteins, which provides a mechanism that allows certain nutrients through the membrane.
Although this mechanism is known to allow the diffusion of many nutrients into eukaryotic cells it is only
known to facilitate the diffusion of glycerol into certain species of prokaryotic microbes. Stereospecific carriers
also mediate active transport, in which the concentration of the transported substrate can be at a much higher
concentration inside the cell. This requires the expenditure of energy to establish a concentration gradient. The
fourth way a nutrient may enter a microbe is through group translocation, in which substrates are chemically
altered to become permeable to the microbes membrane. Compared to active transport, this can save metabolic
energy, as the metabolic energy expended in creating phosphate bonds to allow the substrate to pass through the
membrane is lower than the metabolic energy required to establish a concentration gradient.
The nutrients are then converted to either structural or catalytic elements, with surplus nutrients stored
intracellularly in the form of storage polymers. Catalytic elements may be subdivided into assimilatory and
proliferative machinery [1]. Assimilatory machinery is directly involved in the uptake of nutrients from the
environment and proliferative machinery in the synthesis of genomic and structural macromolecules. The
uptake of nutrients is then dependent on the quantity of assimilatory machinery and the nutrient uptake of each
assimilatory machinery, which is in turn dependent on the environment.
Once a microbe has enough nutrients to build an adequate amount of assimilatory and proliferative machinery
its main goal will be to grow and reproduce. In a suitable environment, microbes reproduce continually and,
in most cases, at a fast rate. When the environment is nutritionally and physically appropriate, a microbe
will undergo unrestricted growth. However, this unrestricted growth will end as soon as there is a change in
environment or the number of microbes increases to a level where the competition for nutrients results in the
restriction of growth. If unrestricted growth occurs long enough then the microbes in the environment will be in
balanced growth, meaning that the time it takes a cell to reproduce will be equal to the time it takes for the cell
to double its content. However, balanced growth very rarely occurs in vitro.

A look at the biological aspects of the papers.

Optimal allocation between nutrient uptake and growth in a microbial trichome.
This paper investigates the optimal allocation between assimilatory and proliferative machinery in [1]. The
allocation of building blocks between assimilatory and proliferative machinery is an extremely important task
for a microbe. Microbes must dedicate enough building blocks to the synthesis of assimilatory machinery to
provide enough nutrients to create an adequate supply of building blocks in the future. In addition, enough
building blocks must be dedicated to proliferative machinery for the cell to continue growing and to repair
damaged components. It was assumed that the nutrients can be taken as a whole, and that the enivornmental
conditions are unchanging. Changing environmental conditions were looked at in detail in [8] and the uptake of
different nutrients in [2].
This paper builds a model using an trichomes. A trichome is a fine outgrowth, found on plants algae
and certain protists [9], that is often the result of the division of epidermal cells [10]. Certain algae, such as
cynobacteria, have their terminal cell produced into a elongate hair-like structure that may either be sheathed, as
in Calothrix, or unsheathed, as in oscillatoria [11]. One use of such trichome is to prevent soil erosion. In plants,
trichomes are found on either the roots or an aerial surface. A primary reason for the presence of trichomes in
plants is to interfere with the feeding of small herbicides.
The first step in explaining this problem mathematically was to use Droop quota model, which states that the
growth rate is dependent on the nutrition provided. The optimal control regime was determined from the Droop
quota model. The optimal allocation regime was divided into before and after a time . When t < , all building
blocks are either allocated towards assimilatory or proliferative machinery, depending on the reserve density of
the microbe. A variable was defined to be the reserve density at which the microbe switches from producing
assimilatory machinery to producing proliferative machinery, in effect switching from the uptake of nutrients to
the growth of the microbe. When the reserve density is lower than the building blocks are allocated towards
assimilatory machinery, resulting in an increase in the reserve density. When the reserve density is higher than
the prescribed value, all of the building blocks are allocated to proliferative machinery, resulting in a decrease
in the reserve density. This leads to the reserve density of the system approaching and remaining close by.
However, when t > , the microbe switches to converting all of its nutrients into proliferative machinery.
This would occur in a starvation phase, when no nutrients are currently available. Therefore, the use of nutrients
in producing assimilatory machinery is pointless as there are no nutrients to uptake. The microbe then allocates
its entire supply of nutrients into producing proliferative machinery to achieve the maximal level of growth,
increasing the chances of the microbe discovering an environment conductive to growth.
One important biological detail is how the microbe knows whether it needs to make more assimilatory
or proliferative machinery. It was suggested that the microbe acquires the information it needs to reach optimal allocation between assimilatory and proliferative machinery by a mixed feedback/feedforward system,

meaning that the microbe receives information from both the inside of the cell and the ambient and acts on
this information to change the proportions between the machineries produced. The change between making
assimilatory and proliferative cells could be done almost instantaneously, with the only delay being the time
it takes the feedback/feedforward system to send the message. However, different nutrients might be needed
for the production of assimilatory and proliferative cells, which could cause a delay as the type of assimilatory
machinery already produced may not be geared towards the uptake of the required nutrient.

Optimal allocation of building blocks between nutrient uptake systems in a microbe.

The cell must also decide on the rate at which nutrients enter and how best to allocate the accumulated nutrients.
To do this it must allocate its assimilatory machinery to the uptake of different nutrients. An important question
posed by [2] relates to the allocation of assimilatory machinery to the uptake of the various nutrients required by
the organism, and in particular, achieving the optimal allocation for the maximal growth rate of the organism.
A simplified model was created to study this problem by assuming the only two elements the microbes need
are nitrogen and carbon, and that the synthesis of only two types of assimilation machinery occur: one that
assimilates a nutrient from which only nitrogen is derived, and one that assimilates a nutrient from which only
carbon is derived. Furthermore, it is assumed that for the synthesis of structural biomass, fixed proportions of
carbon and nitrogen are required and that the microbe converts as much as possible of its nutrient supply [12].
This leads to three possible scenarios. The first is the case of balanced growth, which is achieved when all
chemical quasi-species are growing at the same specific rate [13]. In the case of balanced growth there are no
surpluses of carbon or nitrogen. The second and third cases are the carbon and nitrogen-limited cases, where
the microbe has a surplus of either nitrogen or carbon, respectively. The paper proves that the maximal growth
rate of the cell occurs in the balanced case.
One way for the system to achieve optimal allocation is to include adaptive re-allocation of the cells
assimilatory mechanisms to the uptake of different nutrients. Adaptive re-allocation is where the cell can change
how it allocates its resources to adapt to its needs. If the availability of the ratio of one nutrient to the other drops
then the percentage of assimilatory machinery designated to the uptake of that nutrient increases. Examples
of how transporters may work in different environments is given by Fig. 1. This re-allocation would not be
instantaneous, as it requires new machinery to be created.

A look at the mathematical aspects of the papers

Allocation regimes in microbes happen on a level that is too small to be visible using available microscopy
techniques [14]. Creating mathematical models that closely mimic biological systems is an extremely powerful
way to test hypotheses on allocation regimes. An example of a scenario where a mathematical model can gain

Fig. 1: Adaptive reallocation: It was assumed that the cell requires the same number of nitrogen and carbon per unit of time. Each
panel depicts a microbe, along with its transporters, in a medium containing various amounts of carbon and nitrogen. The top panel
displays nitrogen and carbon in equal abundance, resulting in an equal number of carbon and nitrogen nutrient transporters. The
lower panels display low carbon and nitrogen mediums, resulting in more carbon nutrient transporters and more nitrogen nutrient
transporters, respectively.

otherwise inaccessible information is given by the mechanism for bacterial growth. Although the growth of a
bacteria is visible under a microscope, the mechanisms behind this growth appear invisible [13]. Creating a
mathematical model can allow us to deduce information about the behaviour of this mechanism under different
conditions.

Optimal allocation of building blocks between nutrient uptake systems in a microbe

A mathematical model was created to determine the dynamics of the optimal allocation of building blocks
between different nutrient uptake systems. Care was taken to build this model to mimic physiological conditions,
although in some cases it was necessary to make assumptions to allow a model to be created.
The microbes carbon a nitrogen quotas were defined as QC and QN , respectively. It was assumed that if
the amount of nitrogen is infinite, then the amount of catalytic proteins that were to be synthesized would be
proportional to QC . Assuming the amount of carbon atoms per weight unit of protein is constant, then the
amount of catalytic machinery synthesized can be expressed in C-moles as QC . If C:N is the ratio of carbon
to nitrogen atoms in the protein, then C:N QN represents the amount of catalytic machinery allowed by the
nitrogen quota. The C-molar amount of protein was then taken as the minimum of the two, represented as
Qcata = min{QC , C:N QN }.
To further simplify the model, it is assumed that a fixed proportion (0, 1) of catalytic machinery is
devoted to uptake systems and (1 ) is devoted to other purposes not directly involved in the assimilation of
nutrients. It is also assumed that the machinery not directly involved in the assimilation of nutrients provides
sufficient catalytic capabilities to convert building blocks into catalytic machinery at a rate which permits
Qcata = min{QC , C:N QN } to hold. The effects of varying alpha were explored in the other paper reviewed [1].
Of this proportion , y (0, 1) is devoted to the uptake of carbon, and (1 y) is devoted to the uptake of
nitrogen. This allows the C-molar amount of carbon and nitrogen uptake machinery to be expressed as

MC = yQcata
MN = (1 y)Qcata .
These assumptions lead to the kinetics of the carbon and nitrogen quotas being as follows:

Q C = fC C MC = fC C yQcata
Q N = fC C MC = fN N (1 y)Qcata ,
where fC and fN are dimensionless saturation factors and C and N are uptake rate parameters. These

uptake parameters translate the amount of catalytic machinery in the carbon/nitrogen fluxes that would occur if
the system were completely saturated.
The kinetics were then simplified to

x1 = 1 y
x2 = 2 (1 y),
where
1 =

fC C
fC C + fN N C:N

2 =

x1 = QC

fN N C:N
fC C + fN N C:N

x2 = C:N QN
t 0 = ( fC C + fN N C:N )t.

= min(x1 , x2 )

represents the number of uptake systems, which means the relative growth of microbial is /.
The problem can now be expressed as finding the value of y for which is at its maximum, for some
time T . This can be achieved by the system being in a state of balanced growth, meaning that none of the
carbon and nitrogen is tied up in reserves. When x1 < x2 the microbe is carbon-limited, and when x1 > x2 it is
nitrogen-limited. The phase plane can then be partitioned as follows:

I1 = {x = (x1 , x2 ) R2 : 0 < x1 < x2 }

I2 = {x = (x1 , x2 ) R2 : 0 < x2 < x1 }
I12 = {x = (x1 , x2 ) R2 : 0 < x1 = x2 }.
The alteration of amino acid allocations between nitrogen and carbon transporters was assumed to only
affect transporters that are currently being formed. This is because it is unlikely that prokaryotic microbes
are able to alter machinery that is already in place. Therefore, changing the number of carbon and nitrogen
transporters is reliant on dilution by growth. Therefore, the rate of change of y can be defined to be
d

(y) = u,
dt
where u is ?????, which using the product rule may be rewritten as

y = (u y)/.
The optimal control problem can now be scaled to:

x1 = 1 y(x)

1 > 0

x1 (0) = x10 > 0

T > 0 is fixed

x2 = 2 (1 y)(x) 2 > 0

x2 (0) = x20 > 0

0 < y(0) = y0 < 1

(x(T )) maxu(.)

u(t) [0, 1] t [0, T ]

y = (u y)/

Instating the following feedback control on the optimal control problem results in balanced growth. Let the
feedback control be defined as

0
u(x) =
1

x2 < x1
x2 x1

The feedback regime can then be written as

(i)

lim k = +

k+

lim (k k1 ) = 0

(ii)

k+

(iii)
(iv)

where zi =

xi (x)
(x) ,

lim

max

k+ t[k1 ,k ]

lim

max

k+ t[k1 ,k ]

zi (x(t)) = 0,

i = 1, 2

y(t) = lim

min

k+ t[k1 ,k ]

y(t) = 2 ,

for i = 1, 2 and i are the times at which the system passes from I2 to I1 .

Optimal allocation between nutrient uptake and growth in a microbial trichome

In [1], the creation of the model for optimal allocation between assimilatory and proliferative machinery was
derived from the following equation.


Q0
,
(t) = v(t)m 1
Q(t)
where (t) denotes specific growth, m is the maxima of specific growth, Q(t) is the cell nutrient quota and
Q0 characterises the nutrient quota at which growth vanishes.
The total volume of nutrient in the microbe was defined to be
Q(t)V (t) = Q(0)V (0) + m (Qm Q0 ) f
where V (t) = V (0) exp

Z t

(1 v(s))V (s)ds,

Rt

(s)ds
. The model was then scaled by the following parameters:
0

Q(t) Q0
x1 (t) =
Q0

V (t)
x2 (t) =
V0
8

s
=

Qm Q0
,
Q0

where Qm is the maximum value of Q(t) and f is a characteristic of the environment. This results in the
following model:
x1 = 2 (2 + x1 )v

x2 =

x1 x2
v,
1 + x1

where x1 (t) is the scaled reserve density and x2 is the size of the colony relative to its original size.
If we consider a microbe where > 0 for some fixed time T then at time t > T the environment is not
favourable to the assimilation of nutrients and the cells enter a dormant phase. This dormant phase must be
considered for optimal allocation as well as the active phase. When a cell exits the dormant phase and becomes
active again, the time in the system is reset to 0. When in a dormant phase, the microbe allocates all of its
resources to proliferative machinery, increasing the chances of finding an environment in which it can again
assimilate nutrients. The likelihood of a cell reaching such an environment can be defined as proportional to
x2 (T ) and the optimal regime to be the value of v(t) for which x2 (T ) is maximised. Therefore, the optimal
control problem can be extended by adding the following equations.

x = (x1 , x2 ) R2+ {x1 , x2 > 0}

x(0) = x0 R2+ , x0 (x10 , 1)

v(t) [0, 1] t [0, T ]

J(v) = x2 (T ) max

x(T ) = (x1 (T ), x2 (T )) is free

T > 0 is fixed,

v(.)

where x0 is a given initial condition, > 0 is a constant and v [0, 1] is a scalar piecewise continuous
function.
An optimal control regime, defined as vop (t) where t [0, 1] can be defined as follows.

v (t) if x1 (0) >

1
vop (t) = v2 (t) if x1 (0) =

v (t) if x (0) <

3
1
where

1 if 0 t or t T
1
v1 (t) =

1+ if1 t

x10
1 = ln

x10
2 =
2

1 if 0 t T
v2 (t) =

1+ if1 t



1
= T ln 2 +

v3 (t) =

if t T

1+ if2 t

0 if 0 t
2



x10 x10
1
T? = max{ln
:
} + ln 2 +
.

Now if we let the allocation variable v = v then the scaled nutrient density then
2 (1 v)

x1
= x
v

(1)

and the specific growth rate approaches

vx
.
(2)
1 + x
This is the model for the optimal allocation between assimilatory and proliferative machinery. [1] then goes
on to study this model.

Critique
Both papers build models to mathematically represent allocation regimes in a microbe. In [1], a mathematical
model regarding the optimal allocation between assimilatory and proliferative machinery is created. Mathematical models are always vast simplifictions of real systems and only aim to mimic the system to a satisfactory
level. For a biological system or process to be converted into a mathematical model, assumptions must be made.
All the assumptions made in this paper are sound and the resulting model mimics the biological system as well
as can be expected. A link between growth and available nutrients was modelled by the Droop quota model, before an allocation regime was derived, analysed and proved to be optimal using Pontryagins maximum principle.
A mathematical model for a related allocation problem was derived in [2]. A fixed ratio between assimilatory and proliferative machinery is taken, and looks at the subsequent problems regarding the allocation of
assimilation machinery to the uptake of different nutrients. Further assumptions were then made to simplify
the system, one of which is that the microbe synthesises two types of uptake machinery. One type of uptake
machinery results in the uptake of carbon, and the other in the uptake of nitrogen. Limiting the assimilatory
machinery to two different types allows the creation of a model that still allows us to understand more about
how microbes achieve optimal allocation. Although it does not take into account many other vital elements and
nutrients that will be assimilated by a microbe, this model can still provide interesting insights into how optimal
allocation may work in this instance. The model also overlooks the fact that nutrients are not broken down into
elements but instead into chemical groups. Extending the model to include this would be far too complex.
Other problems include nutrients being able to be broken down into multiple different groups. This problem
was discussed in a previous paper [8] as part of the problem of how microbes achieve balanced growth in
fluctuating environments. This paper predates [2] and suggests working on the allocation problem between
assimilatory and proliferative machinery in the extensions and modifications section. This paper also concludes
that minimal surplus of nutrients are required for balanced growth. However, it suggests scenarios where it is in
the microbes interest to build a surplus of nutrients and how the model can be modified to incorporate this. The
two reasons suggested for creating a surplus of nutrients are the avoidance of a starvation phase and draining

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the environment of nutrients to deprive its competition.

There are many possibilities for further work from both the papers. One possibility would be to create
a model for the optimal allocation of building blocks between assimilatory and proliferative machinery in a
fluctuating environment, in effect combining the work of [1] and [8]. This could be achieved by creating a
model to determine the varible , which is the level of stored nutrients at which the microbe starts to allocate all
of its building blocks to the production of proliferative machinery. When the amount of nutrients is below ,
the microbe devotes its entire store of building blocks to the production of assimilatory machinery. By making
a variable it is possible to vary the distribution of building blocks between assimilatory and proliferative
machinery according to changes in environment.
In summary, these papers efficiently build simple models to create a better understanding how the allocation
of building blocks in microbes may work. Reasonable assumptions were made to allow the creation of these
models, with some simplifications of the biological system required to make the model feasible. The reviewee
has carried out extensive work on optimal allocation in cells, with a handful of insightful papers on the subject.
The papers all tackle different aspects of the microbes workings and together provide a wide overview of
nutrient uptake and cell growth.

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References
[1] Optimal allocation between nutrient uptake and growth in a microbial trichome. van den Berg, HA, et al.,
1998.
[2] Optimal allocation of building blocks between nutrient uptake systems in a microbe. van den Berg, HA, et
al., 2002.
[3] A generic view of classic microbial growth models. van den Berg, HA, 1997.
[4] The classification of organisms at the edge of life, or problems with virus systematics. Rybicki, EP, 1990.
[5] Brock Biology of Microorganisms (13th ed.), Madigan, M, et al., 2006.
[6] An automated comparative analysis of 17 complete microbial genomes. Bansal, AK, 1999.
[7] The structure of the biospheric energy flows. Gorshkov, VG, 1980.
[8] How microbes can achieve balanced growth in a fluctuating environment. van den Berg, HA, et al., 1999.
[9] Plant anatomy. Essau, K, 1965.
[10] Encylclopaedia Britannica. Lotha, G, 2014.
[11] Identify that alga. 2014.
[12] Multiple nutrient limitations in unicellulars: Reconstructing Liebigs law. van den Berg, HA, et al., 1998.
[13] Physiology of the bacterial cell. Neidhardt, FC, et al., 1990.
[14] Magma to microbe: Modeling hydrothermal processes at oceanic spreading centers. Lowell, RP, et al.,
2008.

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