Research progress on microbial transformation of pentacyclic triterpenoids
Bioconversion or biotransformation refers to the process in which exogenous compounds undergo certain biochemical reactions under the action of the organism itself or the catalytic action of active enzymes in the body, resulting in structural changes and the production of valuable compounds. It is also known as biocatalysis. In 1864, Pasteur discovered that Acetobacter could convert ethanol into acetic acid, marking the beginning of the development of microbial transformation technology by humans. In the 1950s, researchers used Rhizopus nigrican to convert progesterone into 11 α – hydroxyprogesterone, marking an important milestone in the history of biotransformation.
Compared to chemical conversion, biological conversion has the advantages of green environmental protection, high catalytic efficiency, mild reaction conditions, and simple subsequent treatment. It can often achieve conversion that is not easy to achieve in chemical conversion such as glycosylation reaction, thereby enhancing biological activity, reducing toxicity, and improving bioavailability. In particular, biotransformation has high regioselectivity and stereoselectivity, and there are also many types of reactions, such as oxidation, reduction, hydrolysis, condensation, hydroxylation, amination, cyclization, acylation, decarboxylation, methylation and demethylation, dehydrogenation, etc., which make it easier to obtain structurally novel compounds and provide more valuable lead compounds for new drug development. However, screening for effective transformation strains among a wide variety of microorganisms remains a huge challenge at present.
Pentacyclic triterpenoids are mainly found in terrestrial higher plants and can be classified into three structural types: ursolic acid type, oleanane type, and lupine type. It has been reported that these compounds have many biological activities, such as anti-cancer, anti diabetes, anti-virus, anti-bacterial and anti-oxidation. Although many medicinal herbs contain pentacyclic triterpenoids, they often have limitations such as low content, low activity, or high toxicity. Through biotransformation, pentacyclic triterpenoids can be transformed into more valuable active ingredients with high activity and low toxicity, or lead compounds with novel structures, laying the foundation for further structural modification and new drug development.

It is not difficult to see from the above research that microbial transformation can transform natural organic compounds into a variety of derivatives, providing more structurally novel compounds for biological activity screening and developing new drugs. There are many types of microorganisms capable of biotransformation, among which fungi are the most commonly studied for the biotransformation of pentacyclic triterpenoids, especially fungi. The reaction types include hydroxylation, carbonylation, hydrolysis, carboxylation, glycosylation, reduction, dehydrooxidation, and acetylation. In fungi, hydroxylation reactions most commonly occur at positions C7, C15, and C21, with significant transformations occurring at positions C1, C2, C23, C24, and C30. A few transformations occur at positions C4, C5, C6, C13, C19, C25, C26, and C29. Carbonylation reactions most commonly occur at the C3 and C21 positions, with a few occurring at the C2 and C24 positions. Esterification reactions occur most frequently at positions C13 and C28, and have also been found at positions C7 and C27. The dehydrogenation reaction is most common at the C11 position and occasionally occurs at the C4, C5, and C23 positions. Carboxylation is also very common at the C3, C29, and C30 positions. The C3, C28, and C30 positions are common sites for connecting glucose, and are most prone to hydrolysis and glycosylation reactions. There are slightly fewer research reports on the transformation of pentacyclic triterpenoids using bacteria than fungi. The most reported research is on bacteria, which mainly involve reaction types such as hydroxylation, carbonylation, glycosylation, hydrolysis, and esterification. These reactions can achieve hydroxylation at positions C2, C1, C7, C15, C23, and C30, as well as carbonylation at position C3. However, in fungi, these types of reactions have not been achieved. Cyclooxidation occurs at positions C11 and C26, cleavage occurs at positions C2 and C3 of the A ring, acetylation occurs at position C1, and carboxylic acid at position C28 is reduced to hydroxymethyl.
The purpose of biotransformation is to convert substrates into more active compounds. Some transformation reactions enhance the cytotoxic activity against tumor cells, such as hydroxylation at C2, C7, and C21 positions, methylation at C28 position, glycosylation at C3 position, and monosaccharide glycosylation at C28 position. These transformation products provide a material basis for screening and studying anti-tumor drug activity. In addition, glycosylation at the C28 position can reduce blood coagulation and provide lead compounds for cardiovascular diseases. Some transformation reactions can enhance anti-inflammatory activity, such as carbonylation at the C3 position, acetylation at the C1 position, hydroxylation at the C1, C7, C15, C21, and C24 positions, and glycosylation at the C3, C28, and C30 positions. Some conversion reactions enhance antibacterial activity, such as glycosylation at the C28 and C3 positions, carbonylation at the C3 position, and hydroxylation at the C21 position, and the resulting derivatives have the potential to develop antibacterial drugs. C29 carboxylation has neuroprotective potential. With the research on biotransformation technology of pentacyclic triterpenoids, a large number of active substances have been discovered, and these new transformation products continue to provide new lead compounds or pharmacological substances for clinical applications. There are numerous types of microorganisms, and further research is needed on how to create new activity value for pentacyclic triterpenoids by screening for biotransformation active strains.
In recent years, the rapid development of enzyme engineering, cell and enzyme immobilization, genetic engineering, fermentation engineering, metabolomics, proteomics, etc., has the potential to integrate multiple genes into the same engineering strain to complete multiple transformation reactions simultaneously, making microbial transformation have a better prospect in drug synthesis.