Key Stage 5
Biology to technology
Student worksheet
Researchers at the University of Oxford are working on using biological
systems to produce chemicals on an industrial scale.
There are two key ways of doing this: living cells can be used as miniature
chemical factories (for example, fungi in fermenters to produce antibiotics)
or enzymes can be isolated from the cells and used in chemical reactions.
Many companies are producing collections of enzymes that are useful for
making chemicals such as drugs, flavours and fragrances. But, there is a
problem: many of these enzymes will not function without an expensive
helper molecule, or coenzyme, called NADH.
NADH - a biological helper molecule
NAD (nicotinamide adenine dinucleotide) is a coenzyme involved in redox
reactions inside cells.
It is found in two forms: NAD+ is an oxidising agent – it accepts electrons
from other molecules and becomes reduced. This reaction forms NADH,
which can then be used as a reducing agent to donate electrons required
for a reaction.
The problem is that NADH is often more expensive than the chemical that
is being produced. So, cheap ways of recharging the NAD+ back to NADH
need to be used so the molecule can be recyled. There is infrastructure
inside cells to carry this out, but when isolated enzymes are used another
method has to be found. Usually this is by using another enzyme.
Your task
You are an industrial chemist who is interested in using an NADHdependent enzyme to catalyse a chemical reaction.
You need to choose a way of recycling NAD+ back to NADH.
There are many different methods available to you. Use page 2 to evaluate
each method (1-3) and choose which one you will use, with reasons.
http://www.oxfordsparks.ox.ac.uk/content/what-can-chemists-learn-nature
Key Stage 5
Method 2
Step A
Biology to technology
How to recycle NADH
hydrogenase enzyme
Step B
Method 1
2eglucose dehydrogenase enzyme
glucose
gluconate
2H+ + 2e-
Hydrogen (H2)
+
NAD+ reductase enzyme
H+
NAD+
NADH
This requires two different enzymes to recycle the NAD+. Hydrogen is used as the
reactant, which is currently produced from fossil fuels.
The leftover H+ is used by the NADH dependent enzyme to reduce the substrate.
NAD+
NADH
This reaction is highly stable.
As with all the methods, the enzymes used are produced by growing cells, usually
on glucose.
No waste products are generated - it has an atom economy of 100%.
Glucose is produced industrially from the breakdown of starch (a food source).
This is a carbon-intensive process which produces a lot of waste products.
Methods that require large quantities of glucose have implications for land use
and food security.
Method 3
formate dehydrogenase enzyme
Glucose is added at very high concentrations (much higher than the starter
chemical), therefore both the excess glucose and gluconate contaminate the
product. They have to be removed and disposed of (usually by burning).
formate
NAD+
carbon dioxide
NADH
The enzyme has a slow turnover frequency.
The waste product, carbon dioxide, makes the solution acidic which affects
the efficiency of the reaction.
http://www.oxfordsparks.ox.ac.uk/content/what-can-chemists-learn-nature
Key Stage 5
Biology to technology
Schematic of HydRegen concept:
Very selective product
> 99 % purity
H2
NADH
NAD+
2eHydrogenase
carbon bead, which conducts the electrons
NAD+ reductase
http://www.oxfordsparks.ox.ac.uk/content/what-can-chemists-learn-nature
Particle
NADH-dependent
enzyme