Features of the Bioconversion of Pentacyclic Triterpenoid Oleanolic Acid Using Rhodococcus Actinobacteria

The ability of actinobacteria of the genus Rhodococcus to transform oleanolic acid (OA), a plant pentacyclic triterpenoid, was shown for the first time using bioresources of the Regional Specialized Collection of AlkanotrophicMicroorganisms (IEGM; WDCM #768;www.iegmcol.ru). The most promising strains (R.opacus IEGM 488 and R.rhodochrousIEGM 285) were selected, and these catalyzed80% bioconversion of OA (0.5 g/L) in the presence of n-hexadecane (0.1% v/v) for seven days. The process of OA bioconversion was accompanied by a gradual decrease in the culture medium pH. Adaptive responses of bacterial cells to the OA effects included the formation of compact cellular aggregates, a marked change in the surface-to-volume ratio of cells, and a significant increase in the Zeta potential values. The results demonstrated that the process of OA bioconversion was catalyzed by membrane-bound enzyme complexes. Participation of cytochrome P450-dependent monooxygenases in the oxidation of the OA moleculewas confirmedusing specific inhibitors. The obtained data expand our knowledge on the catalytic activity of actinobacteria of the genus Rhodococcus and their possible use as biocatalysts for the bioconversion of complex hydrophobic compounds. The results can also be used inthe searchfor promising OA derivatives to be used in the synthesis of biologically active agents. Keywords: bioconversion, oleanolic acid, Rhodococcus, biologically active compound

Biotransformation of Oleanane and Ursane Triterpenic Acids

Oleanane and ursane pentacyclic triterpenoids are secondary metabolites of plants found in various climatic zones and regions. This group of compounds is highly attractive due to their diverse biological properties and possible use as intermediates in the synthesis of new pharmacologically promising substances. By now, their antiviral, anti-inflammatory, antimicrobial, antitumor, and other activities have been confirmed. In the last decade, methods of microbial synthesis of these compounds and their further biotransformation using microorganisms are gaining much popularity. The present review provides clear evidence that industrial microbiology can be a promising way to obtain valuable pharmacologically active compounds in environmentally friendly conditions without processing huge amounts of plant biomass and using hazardous and expensive chemicals. This review summarizes data on distribution, microbial synthesis, and biological activities of native oleanane and ursane triterpenoids. Much emphasis is put on the processes of microbial transformation of selected oleanane and ursane pentacyclic triterpenoids and on the bioactivity assessment of the obtained derivatives

Actinomycetes as Producers of Biologically Active Terpenoids: Current Trends and Patents

Terpenes and their derivatives (terpenoids and meroterpenoids, in particular) constitute the largest class of natural compounds, which have valuable biological activities and are promising therapeutic agents. The present review assesses the biosynthetic capabilities of actinomycetes to produce various terpene derivatives; reports the main methodological approaches to searching for new terpenes and their derivatives; identifies the most active terpene producers among actinomycetes; and describes the chemical diversity and biological properties of the obtained compounds. Among terpene derivatives isolated from actinomycetes, compounds with pronounced antifungal, antiviral, antitumor, anti-inflammatory, and other effects were determined. Actinomycete-produced terpenoids and meroterpenoids with high antimicrobial activity are of interest as a source of novel antibiotics effective against drug-resistant pathogenic bacteria. Most of the discovered terpene derivatives are produced by the genus Streptomyces; however, recent publications have reported terpene biosynthesis by members of the genera Actinomadura, Allokutzneria, Amycolatopsis, Kitasatosporia, Micromonospora, Nocardiopsis, Salinispora, Verrucosispora, etc. It should be noted that the use of genetically modified actinomycetes is an effective tool for studying and regulating terpenes, as well as increasing productivity of terpene biosynthesis in comparison with native producers. The review includes research articles on terpene biosynthesis by Actinomycetes between 2000 and 2022, and a patent analysis in this area shows current trends and actual research directions in this field

Features of the Bioconversion of Pentacyclic Triterpenoid Oleanolic Acid Using Rhodococcus Actinobacteria

The ability of actinobacteria of the genus Rhodococcus to transform oleanolic acid (OA), a plant pentacyclic triterpenoid, was shown for the first time using bioresources of the Regional Specialized Collection of AlkanotrophicMicroorganisms (IEGM; WDCM #768;www.iegmcol.ru). The most promising strains (R.opacus IEGM 488 and R.rhodochrousIEGM 285) were selected, and these catalyzed80% bioconversion of OA (0.5 g/L) in the presence of n-hexadecane (0.1% v/v) for seven days. The process of OA bioconversion was accompanied by a gradual decrease in the culture medium pH. Adaptive responses of bacterial cells to the OA effects included the formation of compact cellular aggregates, a marked change in the surface-to-volume ratio of cells, and a significant increase in the Zeta potential values. The results demonstrated that the process of OA bioconversion was catalyzed by membrane-bound enzyme complexes. Participation of cytochrome P450-dependent monooxygenases in the oxidation of the OA moleculewas confirmedusing specific inhibitors. The obtained data expand our knowledge on the catalytic activity of actinobacteria of the genus Rhodococcus and their possible use as biocatalysts for the bioconversion of complex hydrophobic compounds. The results can also be used inthe searchfor promising OA derivatives to be used in the synthesis of biologically active agents. Keywords: bioconversion, oleanolic acid, Rhodococcus, biologically active compound

Biotransformation of Oleanolic Acid Using <i>Rhodococcus rhodochrous</i> IEGM 757

Using the bioresources of the Regional Specialised Collection of Alkanotrophic Microorganisms (acronym IEGM, Perm, Russia; WFCC # 285), R. rhodochrous IEGM 757 was selected, which catalyzed the C5, C22, and C23 functionalization of pentacyclic triterpenoid oleanolic acid (OA, 3β-hydroxyolean-12-en-28-oic acid, 1.0 g/L) to form a new 5α,22α-dihydroxy derivative of gypsogenic acid (3β,5α,22α-trihydroxyolean-12-ene-23,28-dioic acid) for 5 days. In silico analysis showed that, compared to the native triterpenoid, the OA metabolite may be more soluble in water and less ecotoxic, act as an apoptosis agonist and insulin promoter, and have chemopreventive and analgesic effects. Phase-contrast, fluorescent, scanning, and transmission electron microscopy and X-ray spectroscopy demonstrated the high resistance of R. rhodochrous IEGM 757 to OA. This creates opportunities for further research and development of a method for the production of the OA metabolite. New-generation sequencing of the R. rhodochrous IEGM 757 whole genome, annotation and bioinformatics analysis of the obtained sequences, and real-time PCR were applied. As a result, 24 genes encoding CYP450 enzymes were found, which are highly likely to be involved in the process of OA oxidation