Problem Set 1

QMBT BIO-3615
Due on September 20th 2023
Total points = 5 (5% of total course grade)
Sivert Lundstad

To get full credit you must solve every problem. You may work in teams but by writing your
name on the document, you are acknowledging that you and only you have performed the work
that has been turned in. You must also show all your work to earn points on the problems. It
helps the instructor to provide custom feedback if you provide your name on the on the top of the
problem set.

You can and should read Bruggeman’s Chapter 2.1 – 2.6 and do the exercises and example
problems in the text.
• “Modelling for Systems Biology” by F.J. Bruggeman, VU University, Amsterdam, The
Netherlands, 201; http://bruggemanlab.nl/?page_id=229

1. (5%) Use google scholar to find the article: Bailey, James E. "Toward a science of
metabolic engineering." American Association for the Advancement of Science, 1991.
a) Read the paper and describe your main take always in 300 words or less

James E. Bailys article is a mini review on the advancements made in several

fields related to genetic engineering, gene manipulation and protein synthesis. The
method is usually based on recombinant DNA technology where researchers
introduce heterologous genes into a susceptible host that ultimately should
express the gene, with the hope that the protein is produced faster, with less
resources or/and in a modified form. Advancements in metabolic engineering
could benefit the fields of biopharmaceuticals, biofuels, industrial chemicals,
agricultural biotechnology, and environmental bioremediation.

First example where metabolic engineering has been employed is in the synthesis
of Vitamin C, which normally involves two steps, however when cloning the
enzyme 2,5-DKG reductase into Corynebacterium a redundant step was omitted.

Post translational modifications can also be altered to fit human needs. Expression
of a cloned protein in n Chinese hamster ovary (CHO) resulted in glycoproteins
having sialyl a2,6-galactosyl linkages that more closely resembles what found on
human erythropoietin, which is also a glycoprotein. Erythropoietin is commonly
prescribed to blood cancer patients.

There is several challenges in metabolic engineering at the time this article was
written. Cloning in industrial strains is hard due to the lack of suitable vectors and
methods. Host species may give unanticipated cell responses to genetic
modifications can lead to large cascades of unwanted metabolic changes.
 Regulatory responses may also be activated by the introduction of unnatural
proteins, which in that case also requires the researcher to have knowledge on
how to manage these responses.
Overall, metabolic engineering holds promise for improving bioprocesses and
generating novel products, but it requires a deep understanding of cellular
biology, advanced tools, and iterative optimization processes to achieve success.

b) How many citations does this paper have?

The article has 86 citations according to the PDF.

c) Who was James E. Bailey? What was his affiliation? How is he honored by
bioengineers and quantitative biologists today?

James Edward Bailey was an highly appreciated scientist in the field of

biochemical engineering, whereas he is thought of as a pioneer. Bailey was
affiliated with CalTech from 1980 and until 1992 when he transferred to the
Swiss Federal Institute of Technology (ETH) in Zurich. Bailey has been honored
with several articles written in his honor where he is cherished for the foundation
he made. There is also a Bailey award at Society for Biological Engineering
which “recognizes outstanding contributions in the field of biological engineering.”.

2. (5%) Look up the paper:

Song HS, Lee JY, Haruta S, Nelson WC, Lee DY, Lindemann SR, Fredrickson JK,
Bernstein HC. Minimal Interspecies Interaction Adjustment (MIIA): inference of
neighbor-dependent interactions in microbial communities. Frontiers in microbiology.
2019;10…

…and write a reference for the citation in APA format (hint: try using google scholar!)

(Song et al., 2019)

Song, H.-S., Lee, J.-Y., Haruta, S., Nelson, W. C., Lee, D.-Y., Lindemann, S. R., Fredrickson, J.
K., & Bernstein, H. C. (2019). Minimal Interspecies Interaction Adjustment (MIIA):
Inference of Neighbor-Dependent Interactions in Microbial Communities. Frontiers in
Microbiology, 10. https://doi.org/10.3389/fmicb.2019.01264

3. (5%) Describe the central dogma of molecular biology and list at least one analytical
method used to identify and/or quantify each type of biomolecule in the process.

The central dogma states that genetic information is a flow only going in one direction
starting with DNA, then RNA which is translated to protein, or from RNA directly to
protein. DNA can be identified and quantified with Nanopore sequencing technology.
RNA can be sequenced with PacBio sequencer (iso-seq). proteins can be quantified with
high-performance liquid-based chromatography (HPLC).
4. (5%) Use the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways data base
to view the carbon fixation pathway for photosynthetic organisms (under Energy
Metabolism).

a) List each metabolite that is connected via an enzymatic reaction to “Ribulose-

1,5p2” (Ribulose 1,5 bisphosphate).

Ribulose -5P, H2O, CO2, Glycerate -3P

b) List each enzyme that catalyzes a reaction to and from Ribulose-1,5p2.

Ribulose -5P to Ribulose-1,5p2. Enzyme: Phosphoribulokinase

Ribulose-1,5p2 + CO2 + H2O to Glycerate-3P. Enzyme: ribulose-bisphosphate
carboxylase

5. (5%) Build a drawing (graph) that shows and labels the following growth stages of a cell:
lag-phase, exponential or “log phase”, stationary phase, death or “inhibition” phase
 6. (15%) write a mathematical expression for log phase from your graph/drawing from
Problem 5. Make sure to define each term in your equation and describe its dimensions
(units).
n(t) = n₀ * 2^(t / ). n(t) Is the number of cells at time (t). n₀ os the initial cell count. T is
elapsed time. 2 represents the doubling of cells by each generation.

7. (50 %) Bacterial cells grow exponentially. Typically, we describe “log phase” microbial
growth with the following equation where “X” is biomass concentration, “t” is time

𝑑𝑋
= 𝜇𝑋
𝑑𝑡

a) Solve for X with the knowledge that at t = 0, X = Xo

𝑋 𝑑𝑋 𝑡 𝑙𝑛 (𝑋)
∫𝑋 = ∫0 𝜇𝑑𝑡, Ln(x) – ln(xo) = 𝜇𝑡, 𝑙𝑛 (𝑋 ) = 𝜇𝑡
0 𝑋 0

dX/X = μ dt with μ being of exp growth.

b) What is , what are its units?

μ is the specific growth rate

c) Re-arrange your solution from part a to solve for “time”. Assume that the specific
growth rate is 0.2 h-1 and calculate the doubling time (td)

ln(2)
Given the specific growth rate (μ) of 0.2 h⁻¹, 𝑡𝑑 = = 3.47 ℎours
0.2

d) What is the order of the rate law? How does the rate of biomass change with the
concentration of biomass?

The order of the rate is 1st order, therefore the rate of biomass growth is directly
proportional to the concentration of biomass

e) Do all cells grow exponentially? What could you say about cell growth if you
were given the following rate law that describes a “zero order reaction”?
𝑑𝑋
= 𝜇𝐶
𝑑𝑡
Not all cells grow exponentially, which the graph also illustrate. Growth in this
case would be stagnant and linear.

f) Solve the equation from Part e using the same initial conditions from Part a. What
are the dimensions (units) for the growth rate here
𝑋 𝑡
∫𝑋 𝑑𝑥 = ∫0 µ𝐶 𝑑𝑡, X – Xo = µ𝐶 𝑡, 𝑋(𝑡) = µ𝐶 𝑡- Xo
0
Units: biomass concentration units divided by time

g) Draw or computationally generate plots to compare how “X” (Y-axis) changes

with “t” (X-axis) between the two cell growth models that you have been given
(parts a and e, respectively).

8. (10%) See Rmarkdown Project “1.QMBT.Rproj.rmd”

Done☺