Biocatalysis
An enzyme produced by a microbial organism within its own biochemical pathways in metabolism that can be retrieved and utilized as a catalyst within synthetic chemical reactions.
Biocatalysts are chosen based on their regioselectivity for the target molecule and the ability to utilize their natural biochemistry in the generation of novel biosynthetic pathways tailored towards the reaction at hand (Bell 2021). Given the wide array of microbial species, there is a large selection of biochemical pathways for enhanced regio-specificity.
What is a biocatalyst?
Why do pharmaceutical reactions rely on catalysis?
Pharmaceutical reactions are often lengthy, with several workup steps involved to yield the highest-purity product, and the products are highly complex molecules.
Due to the extensive nature of these reactions, they require a myriad of bulk chemicals and highly selective catalysts to reduce the number of steps required and speed up the reaction.
What are the environmental impacts of the pharmaceutical industry?
Climate Change
As the pharmaceutical industry is widely used and globally relied upon, the further expansion of this industry has contributed significantly to greenhouse gas emissions. This GHG contribution is so large that this industry alone has an impact on further climate change and global warming (Booth 2023). GHG emissions from the pharmaceutical industry are not only from the transportation of drugs, as well as the production of plastics for pharmaceutical packaging, but also most notably from the emissions produced by the reactions themselves. These industrial-scale chemical reactions contribute to greenhouse gas emissions through the release of greenhouse gases as reaction byproducts in exhaust systems, but also through the large energy input required to power these reactions (Booth 2023).
Chemical Waste
Workup steps from these reactions often involve the use of bulk chemicals that can not only be harmful to the environment when disposed of, but also harmful to those exposed to said chemicals. Many of these wastes contain volatile organic compounds and highly toxic chemicals that are released from exhaust systems into the atmosphere, thus putting public health at risk and polluting the air (Bahmani 2025). Medical waste from pharmaceuticals also contains potentially toxic elements, carcinogens, and endocrine disrupters, which further exacerbate these negative impacts. The pharmaceutical industry also contributes to the release of fine particulate matter into the atmosphere, which is connected to further morbidity of disease as well as smog formation (Bahmani 2025).
Pollution of Water Sources
Due to the several workup steps that are required to synthesize pharmaceutical compounds, many of these steps generate excessive chemical waste and wastewater that are often improperly disposed of. Improper disposal causes leaching into groundwater, which can lead to trace concentrations of pharmaceutical waste in drinking water and surrounding aquatic ecosystems (Patneedi 2008). Common pharmaceutical compounds such as antibiotics, NSAIDs, and more have even been found in municipal drinking water sources at higher concentrations. This not only increases the likelihood of antibiotic resistance (and thus more widespread prevalence of resistant infectious diseases), but also negatively impacts surrounding wildlife and damages nearby ecosystems (Patneedi 2008).
Biocatalysis Mighty Microbes
Bacillus subtilis
Bacillus subtilus is often used as a model organism in biochemical studies concerned with enzyme retrieval. Their effective protein display for enzymes and spore formation makes them easily studied for biocatalysis, as their proteins are highly stable for retrieval and immobile in nature (Farinas 2024). Their stability makes them highly reliable for pharmaceutical catalysis on an industrial scale (Farinas 2024). The enzyme produced by B. subtilis, lipase, is particularly attractive for biocatalysis use as it is highly regioselective, which is a major requirement for pharmaceutical reactions. Lipases derived from B. subtilis are also resistant to environmental changes, which makes them useful for several reaction steps and changing reaction environments (Guncheva 2011). Bacillus subtilis is also easy to obtain and genetically modify; therefore, it enhances catalysis processes on a commercial scale due to its wide distribution and ability to modify selectivity (Danilova 2020).
Industrial scale biocatalysis, Stable protein formation
Endophytic Fungi
Endophytic fungi are found in nature as endosymbionts with several plant species, making up a crucial part of the plant microbiome as they produce several different secondary metabolites that have already been widely used within the pharmaceutical industry (Singh 2023). Their enzymatic cascades have also proven useful in increasing the regioselectivity of pharmaceutical reactions, successfully reducing the consumption of bulk organic solvents as well as their associated chemical waste. Endophytic fungi have a large range of enzymes produced in their own catalytic reactions, therefore representing a larger range of new opportunities and applications to diverse complex pharmaceutical compounds as well (Choudhary 2021). A large range of biotransformation reactions have also been identified using endophytic fungal enzymes as the biocatalyst, which have been utilized within pharmaceuticals to generate higher yield and higher purity products while reducing dependence on traditional catalysts that generate increased chemical waste (Borges 2009).
Increased regioselectivity, Reduced chemical waste
Pseudomonas spp.
Species of Pseudomonas have also been researched with application to the pharmaceutical industry, in particular their lipases, which can act as biocatalysts for a range of pharmaceutical reactions on an industrial scale. Lipases can be used as successful commercial biocatalysts due to their high stability, selectivity, and substrate versatility (Rios 2018). Species within the Pseudomonas genus have also cut down the length of pharmaceutical reactions by eliminating the need for advanced purification. This is due to their enzymatic ability to generate pure pharmaceutical compounds that needn't undergo the vigorous workup steps associated with traditional pharmaceutical catalysis (Molina 2013). This is attributed to the enhanced enantioselectivity of the esterase and lipase enzymes produced by Pseudomonas enzymatic pathways (Wu 2015). The stability of Pseudomonas under adverse environmental conditions, such as potentially inhibiting chemical solvents, also aids in its ability to act as a successful biocatalyst, as many pharmaceutical reactions require exposure to these chemicals (Becker 2012).
