Bio-Economy and Technology: The Challenges of Industrial Fermentation

Blog The Challenges Of Industrial Fermentation
Laboraty fermenter used in industrial fermentation to cultivate microorganisms
Microbial fermenter

In a previous blog about industrial fermentation, we defined traditional fermentation and industrial fermentation and gave examples of applications. Human beings have been experimenting with fermentation for thousands of years. However, bringing fermentation to an industrial scale is not that simple. There are numerous challenges facing industrial companies from technical barriers to regulation. In this blog, we will discuss some of these challenges and give you an insight into the complexity of this technology, starting with some technical barriers.

Fermentation is a biological process. This means that several parameters in the fermenter can cause a failure in production. Let’s discuss some of the bottlenecks of the fermentation process

Raw materials purity

The lack of purity of the raw materials to ferment or the presence of stress-inducing chemicals in the medium: This is a common issue in biofuel production. Most microorganisms will be inhibited by the presence of alcohol or organic acids, two components generally involved in the process.

Competition in the fermenter

The presence of undesirable competitive microorganisms or phages in the fermenter: This can result in partial or complete loss of production. Industrial fermentation requires a sterile production environment.

Product inhibition

Product inhibition is also a technical barrier to consider: It is a type of enzyme inhibition where the product of an enzyme reaction binds to the enzyme and inhibits its activity. For example, Newlight Technologies is a company who produces a bio-plastic called AirCarbon. It has taken them nearly 10 years to “develop a biocatalyst that does not “turn itself off” based on the amount of polymer being produced”.

Microorganisms intrinsic limits

The inability of microorganisms to process economically viable raw materials: An example is the production of vanillin by fermentation. Various precursors to the vanillin biosynthesis pathway in microorganisms can be used, such as eugenol or ferulic acid. Ferulic acid can be recovered from agricultural plant waste, which constitutes a cheap starting material for bio-production. However, the recovery of ferulic acid from plant cell walls appears to be somewhat complicated and costly.

Recombinant strains of bacteria, fungi, and yeasts represent an interesting alternative to wild-type strains, and a diverse set of methodologies has been developed to engineer and optimize the bioconversion of various precursors to vanillin. BASF and Conagen are among the organisations developing such microorganisms industrially:

Other bottlenecks can emerge such as inefficient metabolic flow, costly downstream processing methods due to the physicochemical properties of the substrate and the product, and further metabolism of the desired product by the selected microorganisms.

All these technical issues can indirectly affect the costs by impacting production schedules and product quality or by involving additional stages of research and development. As a key technology in the bio-economy, industrial fermentation must also respond to sustainability and regulatory pressures.

We will look at these in our next blog: How Sustainability and Regulation Affect Industrial Fermentation

Other resources you might like:

Bio-economy and Technology: From traditional to industrial fermentation

Blog Bio-economy and Technology: From traditional to industrial fermentation
Vintage copper kettle in brewery - Belgium
Vintage copper kettle in brewery – Belgium

Man has used fermentation for thousands of years. Today, the principles of fermentation are applied to industrial processes and it is a key technology within the bio-economy, providing us with a wide array of sustainable chemicals from biofuels to cosmetics.

What is “traditional fermentation”?

Fermentation has been part of our daily lives since simple microbes were first ‘domesticated’. It has been one of man’s earliest food preservation technology used for centuries prior to the discovery of pasteurization and sterilization.

Every culture has a variety of fermented food and drink as part of its diet. It is a relatively cost‐effective, low‐energy preservation technique, essential to extending shelf life and ensuring food safety. You will come across it every day when you consume bread, sausages, yogurt, wine or beer, for example.

What is “industrial fermentation”?

The bio-economy has evolved with the development of molecular science and cell biology. Consequently, sub-sectors have evolved such as biotechnology, biofuels and green chemistry. In the media, industrial fermentation is largely associated with bioenergy and bioplastic solutions. Industrial fermentation is also used in life science, food & drink, cosmetics, and others.

Industrial fermentation is a biotechnological process based on the exploitation of cells to produce the desired end-product. This might include molecules like organic acids, amino acids, vitamins, enzymes, antibiotics, biopolymers or others. The cell may be a bacterium, a yeast, an alga, or more complex such as a mammal cell (the most used is CHO – Chinese Hamster Ovary cell).

Colonies of bacteria growing on a Petri dish
Colonies of bacteria growing on a Petri dish

The aim is to produce these useful molecules on a large scale. Using ‘simple’ microorganisms enables us to produce simple molecules, such as ethanol by yeast or lactic acid by bacteria. More complex microorganisms such as mammal cells are used in the life science industry to produce more complex chemicals like antibodies or drugs.

Industrial fermentation requires various disciplines: microbiology, genetics, biochemistry, chemical engineering, synthetic biology among others. So, companies need to access an appropriate range of skills and techniques to be successful in developing products through fermentation.

Common industrial fermentation applications

As mentioned earlier, the range of applications is almost infinite. Many industries develop their products using fermentation technology. Here are a few examples of products on the market using industrial fermentation:

  • Food: Quorn Foods and 3F Bio produces mycoproteins, a variety of protein obtained by fungal fermentation and used in meat-free products
  • Animal Feed: Veramaris, a joint venture between DSM and Evonik, uses marine microalgae to ferment omega-3 fatty acids (EPA and DHA) for animal nutrition, especially aquaculture
Microalgae in laboratory tubes
Microalgae in laboratory tubes
  • Cosmetics: Metabolic Explorer, via its subsidiary METEX NØØVISTA, produces 1,3 Propanediol (PDO) by industrial fermentation. The company has recently signed a partnership with DSM to market this molecule to the cosmetic ingredients market
  • Bioplastics: Danimer Scientific uses bacteria to ferment polyhydroxyalkanoate (PHA), a polymer found in bioplastics

These examples are just the tip of the iceberg.  When you see how much can be done with technologies such as industrial fermentation, the possibilities are truly exciting.

Many challenges can hinder the development of new products by industrial fermentation, not least return on investment. We will look at some of the more common challenges in our next blog.

Follow us to keep up with the latest news in industrial fermentation (and other biotech sectors):

Scientific names of microorganisms: Why should you care about taxonomy?

Blog Why should you care about the scientific names of microorganims
Scientific names of microorganisms. R&D, Innovation, Marketing, New Product Development

Scientists have discovered an incredible amount of microorganisms such as bacteria, yeast or microalgae. To differentiate them from each other, they name them scientifically following strict taxonomic rules. But why should you care about the scientific names of microorganisms and where can you find this kind of information?

You may know that the scientific names of microorganisms can evolve over time. If you are not aware of this, check out our blog on the definition of taxonomy and why it evolves over time.

When your research and development projects involve the use of microbes, you have to get your head around taxonomy. Why and how? This is what we discuss in this blog.

Three reasons why it is essential to verify the scientific name(s) of microorganisms

Far from being a waste of time, checking out all the synonyms used to name the microbes you are studying is essential. It will allow you to avoid confusion or missing information. It may even help you to tackle some obstacles with regulations.

Avoid confusion

Certain microorganisms possess a common name to describe their usage, their origin or behaviour. One well-known example is ‘baker’s yeast’.

Did you know that the baker’s yeast, whose scientific name is Saccharomyces cerevisiae, is also commonly called “brewer’s yeast”?

Vintage copper kettle in brewery - Belgium
Vintage copper kettle in brewery – Belgium

Did you also know that it is common to see “baker’s yeast” confused with “baking powder”? This is generally due to a lack of knowledge about breadmaking. It may also be the result of the popular use of the name “chemical yeast” (also called “baking powder” or “raising agent”).

There is little chance of finding this kind of mistakes in patents or scientific publications, exception made for some rare mistranslations (generally of Asiatic languages).  But when performing a prior art search for patentability, for example, all types of documents in the public realm must be searched. This is when you risk encountering such imprecise vocabulary.

Therefore, I would always recommend including the full scientific names of microorganisms in your literature review.

Names that relate to the end-use or inexact popular science demonstrate the need to be precise at different levels with the names of microorganisms that we study.

Be ‘exhaustive’ in your literature review

If you have already tried researching scientific papers or patents in databases (free or paid), you will no doubt have noticed that using precise keywords is crucial to compiling a thorough bibliography.

When you undertake a literature review including the concept of microorganism, it’s essential to research the evolution in naming microorganisms beforehand.

Let’s return to our example Saccharomyces cerevisiae.

In 1923, Henri Boulard isolated a yeast strain called Saccharomyces boulardii, which is nowadays commercialised as a probiotic. This strain has been defined variously along taxonomic, metabolic and genetic lines. Then, with the evolution in techniques to identify microorganisms, researchers noticed that Saccharomyces boulardii shares more than 99% of genetic similarities with Saccharomyces cerevisiae whilst displaying different characteristics (phenotype).

A person holding a bottle of probiotic capsules
Human health & wellbeing – Probiotic capsules

Since then, the debate continues as to whether Saccharomyces boulardii is a distinct species or a subspecies of Saccharomyces cerevisiae.

So, how does this impact your literature research?

If you limit your keyword search to « Saccharomyces cerevisiae boulardii », you may miss documents referring to this same strain in the following ways :

  • « Saccharomyces cerevisiae var boulardii »
  • « Saccharomyces boulardii »
  • « S. cerevisiae boulardii » (it is customary to use the first letter of the genus of microorganism)
  • « S. cerevisiae var boulardii »
  • « S. boulardii »
  • « boulardii »

If you analyse the development in taxonomy of the microorganisms you study, it is very likely that you will find a list of synonyms to use in your own literature research.

A matter of regulations

In agribusiness as in health and nutrition applications, adding microorganisms to products coming into direct and indirect contact with humans is highly regulated.

Let’s imagine that your company has exploitation rights to a microorganism which looks promising for food applications. Nevertheless, this microorganism forms part of a regulated list which prevents you from applying it to foodstuffs. You may have to spend time and money compiling regulatory documents with no certainty of success.

Researching the taxonomy can decide the fate of your R&D or New Product Development projects.

A comprehensive taxonomic analysis could be beneficial to your project by:

  • Proving that a microorganism belongs to a species or a genus permitted for nutrition
  • Detecting any public document stating the consumption of a microorganism by the general population before the regulation in place
  • Finding any scientific documents citing a microorganism under synonyms and proving it is harmless to consume.

In the end, if you discover that the microbe of interest is not authorised for the application you target, then you’ll have saved time and money by not pursuing this project.

Where can you check out the scientific names of microorganisms?

Now that you know why it is crucial to verify the taxonomy of microorganisms for your scientific research, here are a few online resources for you to start with :

  • Yeasts :
  • Bacteria : EZBioCloud – Fast search engine
  • Algae: AlgaeBase – ‘AlgaeBase.org’ declares that their database is purely meant as an aid to taxonomic studies and not a definitive source in its own right.
  • All microorganism: NCBI – Database that centralises various microorganism and points out other reliable sources of information

You can also check out the online catalogs of strains collections around the world such as the NCIMB in the UK or the DSMZ catalog in Germany for example. You may not find all the required information about taxonomy in these databases but you will access to valuable data to cross-check references.

Although the subject may seem complex and the task onerous, it is worth exploring the taxonomy of the microorganisms you intend to use in your R&D, Innovation and NPD projects. Indeed, you will be able to save time by compiling the necessary information relating to these microorganisms.

In a world where there is never enough time or money, knowing how to embark upon your projects with the right microorganism and/or make use of existing resources for other applications can be a real winning strategy.

Scientific names of microorganisms: A quick introduction to taxonomy

Blog Introduction to Taxonomy
Taxonomy. Knowledge and plan concept

When I embarked upon my career in the fermentation industry, I was surprised by the complexity surrounding taxonomy or more simply put, the scientific names of microorganisms.  In the same way as human history, the taxonomy of microorganisms is not linear. The only constant is change.

Thanks to scientific discoveries and the evolution of biotechnology, researchers are regularly reclassifying and renaming bacteria, yeasts, and other microorganisms. This impacts my work, and probably yours, for different reasons.

In this blog, I will paint a quick picture of the taxonomy of microorganisms and why it evolves.

How microorganisms are named by the scientific community?

Taxonomy is a discipline in biology. It aims at describing living organisms and regrouping them in order to identify, name and classify them.

Each microorganism has a unique, specific name. This nomenclature is overseen by committees and with different rules according to the microorganisms :

These organisations are collaborating with the scientific community to create a standardized nomenclature. Scientists can make proposals for a new taxonomy based on evidence from their research.

The scientific name of microorganisms is written in Latin. It is made up of two parts: genus and species.

Let’s take baker’s yeast as an example:

Saccharomyces [genus] cerevisiae [species]

Saccharomyces cerevisiae yeast, 3D illustration
Saccharomyces cerevisiae yeast, 3D illustration

Classification can go as far as strain or variant so as to differentiate between microorganisms who show different variations of observable behaviour (called ‘phenotype’ in scientific language).

Staying with our baker’s yeast:

Saccharomyces [genus] cerevisiae [species] var cerevisiae [strain]

But another strain of S. cerevisiae could be:

Saccharomyces [genus] cerevisiae [species] var boulardii [strain]

The two strains are nearly identical at a molecular level but Saccharomyces cerevisiae boulardii shows more physiological resistance to heat and acidic stress. Saccharomyces boulardii and Saccharomyces cerevisiae are two closely related strains used either as a probiotic or in the preparation of food and wine. 

Why is the taxonomy of microorganisms evolving over time?

The naming of microorganisms evolves and is closely linked to scientific progress, notably genetic analysis methods. The graph below, created by EzBioCloud, shows the correlation between the genetic sequencing of bacteria and archaea and the number of new species in scientific journals. Among these new species, some already existed under other names.

Correlation between the genetic sequencing of bacteria and archaea and the number of new species in scientific journals - EzBioCloud.
Extract from EzBioCloud dashboard – 18/12/2019

EzBioCloud publishes a dashboard showing the genetic diversity and taxonomy of bacteria and archaea. It is quite complete and regularly updated.

Without going into too much detail of the genetic techniques, here are some of the other factors that can lead to the reclassification of microorganisms:

  • Taxonomy: a global review of the rules pertaining to taxonomy can be the origin of important changes (1) (2).
  • Behaviour: by exposing microorganisms to new environments, scientists can discover previously unknown variations in phenotype.
  • Structure: the observable morphology of microorganisms has an impact on their classification. This factor can vary, depending on the stage of microorganism development throughout their study by scientists.
  • Interaction with humans: when a microorganism comes into contact with us, it can show different behaviour not always observed beforehand.

This list is not exhaustive but shows just how far taxonomy is a living, evolving field of research. It is important to know when and how to check this taxonomy. Indeed, this information can influence the success or failure of your research and development projects.

In our next blog, you will get to know why you should care about the scientific names of microorganisms and how to check them out.

(1) “An Update on the Novel Genera and Species and Revised Taxonomic Status of Bacterial Organisms Described in 2016 and 2017”; Erik Munson, Karen C. Carroll; Journal of Clinical Microbiology Jan 2019, 57, 2: e01181-18; DOI: 10.1128/JCM.01181-18
(2) “A history of research on yeasts 8: taxonomy”; James A. Barnett; Yeast 2004; 21: 1141–1193; DOI: 10.1002/yea.1154

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