Microorganisms in Biotechnology

Spec Mapping — OCR H420 Module 6.2.1 — Cloning and biotechnology, content statements covering the use of microorganisms (bacteria, yeast, filamentous fungi) in food production (brewing, baking, dairy fermentation, mycoprotein), in pharmaceutical production (penicillin, recombinant therapeutic proteins), the distinction between primary and secondary metabolites, and the advantages and disadvantages of microbial biotechnology compared with plant- and animal-derived alternatives (refer to the official OCR H420 specification document for exact wording). This lesson pairs with the culturing-microorganisms lesson that follows.

Biotechnology is the use of living organisms, cells or cell components to produce useful products. Microorganisms — bacteria, yeasts and fungi — are the workhorses of biotechnology because of their rapid growth, genetic flexibility, and ability to synthesise complex molecules in large quantities. OCR A-Level Biology A specification 6.2.1 requires you to know the roles of microorganisms in food production, brewing and pharmaceuticals, and to evaluate their advantages and disadvantages.

Industrial-scale microbial biotechnology dates from the early twentieth century but accelerated dramatically with the wartime push to mass-produce penicillin. Alexander Fleming's chance observation in 1928 at St Mary's Hospital London — that a contaminating Penicillium colony on a Staphylococcus plate created a halo of inhibited bacterial growth — gave the discovery, but it was the deep-tank fermentation work led by Howard Florey and Ernst Chain at Oxford and by the US Department of Agriculture's Northern Regional Research Laboratory in Peoria, Illinois (1941-44) that converted penicillin from laboratory curiosity to mass-produced antibiotic. Fleming, Florey and Chain shared the 1945 Nobel Prize in Physiology or Medicine. The wartime fermentation infrastructure — submerged-culture fermenters with mechanical agitation and forced aeration — became the template for every subsequent industrial microbial process. Paraphrased: the penicillin programme established the engineering principles (sterility, stirred tanks, oxygen-transfer rate, downstream purification) on which the modern biopharmaceutical industry still rests.

Key Definitions:

• Biotechnology — the industrial use of living organisms or their products.
• Fermentation — anaerobic metabolism by yeast or bacteria producing useful products (ethanol, lactic acid, CO₂).
• Primary metabolite — a substance produced by a microorganism during normal growth (e.g. ethanol).
• Secondary metabolite — a substance produced after the main growth phase, often under stress (e.g. penicillin).
• Single-cell protein (SCP) — protein produced by microorganisms for human or animal food.

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Why Use Microorganisms?

Microorganisms have several advantages over plants and animals for producing useful substances:

• Rapid growth — bacteria can double every 20–30 minutes; animals take years.
• Cheap substrates — many microorganisms grow on waste materials (molasses, whey, cellulose).
• Controlled conditions — temperature, pH and nutrients can be precisely regulated in a fermenter.
• No ethical issues compared to animal products.
• Easy genetic manipulation — GM bacteria can produce human proteins (Lesson 2).
• High yields — vast quantities of product from small fermenters.
• No seasonal limitations — year-round production independent of climate.
• Can be used in developing countries — no refrigeration needed for fermented foods.

Disadvantages include the need for aseptic technique to prevent contamination, careful downstream processing to purify products, and sometimes consumer suspicion of microbial origin.

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Food from Microorganisms

Brewing and Wine-Making

Humans have fermented beer and wine for over 10,000 years — archaeological evidence from Jiahu in China places brewed-rice fermentation at around 7000 BCE, and the domestication of Saccharomyces cerevisiae probably preceded that of any food crop other than the earliest cereals. Both beer and wine rely on yeast (Saccharomyces cerevisiae for beer and most wine; S. ellipsoideus / S. cerevisiae var. ellipsoideus for traditional wine) converting sugar to ethanol and carbon dioxide anaerobically:

$\text{C}_6\text{H}_{12}\text{O}_6 \rightarrow 2\text{C}_2\text{H}_5\text{OH} + 2\text{CO}_2$C6​H12​O6​→2C2​H5​OH+2CO2​

• Beer is made from malted barley. Malting germinates the barley, activating amylase which hydrolyses starch to maltose. The resulting "wort" is boiled with hops (for bitterness and preservation), cooled, and fermented with yeast for about a week. Lager uses bottom-fermenting yeast at low temperature; ale uses top-fermenting yeast at higher temperature.
• Wine is made from grape juice, which already contains sugar and wild yeast on the skins. Modern wine uses cultured yeast strains for consistency. Fermentation takes 1–2 weeks, followed by months to years of maturation.
• Spirits (whisky, gin, vodka) are produced by distillation of fermented liquids, concentrating the ethanol well above 12–15% (the tolerance limit of yeast).

Baking

Bread dough contains yeast, which ferments the sugars in flour. The CO₂ produced becomes trapped by the gluten network, making the dough rise. The ethanol evaporates during baking. Fast-action dried yeast is a selected strain of S. cerevisiae.

Cheese

Cheese-making uses lactic acid bacteria (Lactobacillus, Lactococcus, Streptococcus) to convert lactose in milk to lactic acid, lowering the pH. This causes the milk protein casein to coagulate. Rennet (containing chymosin — now usually produced by GM microorganisms, marketed as Chy-Max or Maxiren) accelerates coagulation; recombinant chymosin from GM Aspergillus, Escherichia coli or Kluyveromyces was the first commercial GM food enzyme, approved in 1990, and now dominates the global supply. Before recombinant production, chymosin came from the fourth stomach of unweaned calves — a supply problem that limited cheese production and made vegetarian cheese impossible. The curds are separated from the whey, pressed and aged for periods ranging from a few weeks (mozzarella, brie) to several years (parmigiano reggiano, comté). Specific secondary cultures give characteristic cheese flavours: Penicillium roqueforti (Roquefort, Stilton — blue-veined cheeses), P. camemberti (Camembert, Brie — white-rinded cheeses), Propionibacterium freudenreichii (Swiss / Emmental cheese and its holes from CO₂ release during fermentation), and Brevibacterium linens (the orange surface of washed-rind cheeses such as Munster).

Yoghurt

Yoghurt is made by adding Lactobacillus bulgaricus and Streptococcus thermophilus to warm milk (40–45 °C). The bacteria ferment lactose to lactic acid, which curdles the milk protein and gives the characteristic tart flavour. Probiotic yoghurts add Lactobacillus acidophilus and Bifidobacterium for claimed gut-health benefits.

Vinegar

Acetobacter bacteria oxidise ethanol (from wine or cider) to acetic acid, producing vinegar.

Soy Sauce and Miso

Traditional Japanese foods are fermented with Aspergillus oryzae (a mould), followed by lactic acid bacteria and yeast, over months.

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Single-Cell Protein: Mycoprotein (Quorn)

Mycoprotein (trade name Quorn) is a meat substitute produced by fermenting the fungus Fusarium venenatum in huge continuous fermenters at Billingham, County Durham. The fungus is grown on glucose syrup (typically from wheat starch) with added ammonia (nitrogen source) and mineral salts at 28–30 °C and pH 6.

Product	Microorganism	Substrate	Mode	Key use
Bread	Saccharomyces cerevisiae	Flour sugars	Batch (dough)	Leavening
Beer	Saccharomyces cerevisiae	Malted barley wort	Batch	Ethanol + CO₂
Wine	Saccharomyces cerevisiae / ellipsoideus	Grape sugars	Batch	Ethanol
Cheese	Lactobacillus, Lactococcus, Streptococcus, Penicillium	Milk lactose	Batch	Lactic acid, flavour
Yoghurt	L. bulgaricus, S. thermophilus	Milk lactose	Batch	Lactic acid
Vinegar	Acetobacter	Ethanol	Continuous (trickling filter)	Acetic acid
Quorn (mycoprotein)	Fusarium venenatum	Glucose syrup + ammonia	Continuous	Single-cell protein
Penicillin	Penicillium chrysogenum	Corn-steep liquor + glucose	Batch (secondary metabolite)	Antibiotic
Insulin	GM E. coli / GM S. cerevisiae	Glucose + amino acids	Batch	Biopharmaceutical
Citric acid	Aspergillus niger	Molasses	Batch	Food acidulant
Biofuel ethanol	S. cerevisiae	Cane/maize sugars	Continuous	Fuel

After harvesting, the mycelium is heated to reduce its RNA content (high RNA intake produces excess purine catabolism and elevated serum urate, potentially precipitating gout in susceptible individuals), mixed with egg white (or potato starch in vegan versions) as a binder, flavoured and formed into "meat" shapes. The continuous-fermentation infrastructure at Billingham is the largest of its kind in the world, with airlift fermenters of around 150,000 L capacity running 24 hours a day. Continuous mode is appropriate because mycoprotein is a primary metabolite — the Fusarium biomass itself is the product — and continuous-mode steady-state log-phase growth maximises volumetric productivity. The medium is carefully balanced to limit any single nutrient, ensuring that growth remains carbon-limited and that the fungus does not switch to secondary metabolism (which would risk mycotoxin production, hence the rigorous selection of F. venenatum strain ATCC 28036 / IMI 145425 as the production isolate after extensive toxicity screening).

Advantages of mycoprotein:

• High in protein (45% dry weight) and dietary fibre.
• Low in fat and cholesterol.
• Amino acid composition similar to animal protein.
• Grown much faster than livestock.
• Far lower greenhouse gas emissions than beef.
• Land-efficient — about 1/20th the land area of beef per kg protein.

Disadvantages:

• Some people are allergic to Fusarium.
• Requires careful control and expensive fermenters.
• Cannot match exact texture of all meats.
• Some consumers are wary of "fungus food".

Quorn has been sold since 1985 and now has annual sales of over £200 million.

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The Industrial Fermenter (Bioreactor)

Industrial-scale microbial cultivation takes place in stirred-tank bioreactors — sealed vessels of typical working volume 10,000-200,000 L containing a sterile growth medium, mechanical agitation, temperature control, aeration, and sampling ports. The engineering challenges centre on maintaining sterility, dissipating metabolic heat, supplying oxygen at the rate the culture demands, and keeping the suspension homogeneous.

Batch vs continuous fermentation

flowchart TD
    A[Choice of fermentation mode] --> B{Primary or secondary metabolite?}
    B -->|Primary, eg ethanol, mycoprotein| C[Continuous fermentation]
    C --> D[Steady-state culture in log phase]
    D --> E[Constant nutrient feed + product removal]
    E --> F[High volumetric productivity]
    B -->|Secondary, eg penicillin, antibiotics| G[Batch fermentation]
    G --> H[Closed system, single growth curve]
    H --> I[Lag → log → stationary → decline]
    I --> J[Product harvested at end of stationary / decline]

The choice between batch and continuous fermentation is dictated by metabolic biology: secondary metabolites (penicillin, antibiotics, statins, cyclosporin) are produced under nutrient stress in late culture and require the batch growth curve; primary metabolites (ethanol, lactic acid, citric acid, mycoprotein) are produced throughout log growth and benefit from continuous-mode steady state. Fed-batch is a hybrid: a batch culture with periodic supplementation, used for recombinant insulin and most modern biopharmaceuticals to maximise cell density before induction of product expression.