Fig. 4 UA derivatives modified on ring A
4.2Directed transformation of UA by microorganisms
Biosynthesis of valuable products have advantages over chemical synthsis in terms of milder reaction conditions and presence of abundant enzymes along with high stereo-, regio- and chemo- selectivities53. Therefore, microbial transformation is increasingly adopted as an alternative way to modify the structure of natural and synthetic compounds 54,55. In particular, it is easy to achieve the glycosylation of pentacyclic triterpenes that is difficult during chemical synthesis 56. Generally, UA biotransformation is carried out by dissolving the appropriate quantity of UA in strain suspended in fresh sterile broth under sterile conditions. After co-cultivation with strains, the transformed products of UA are eventually separated through suction filtration and extraction.
In recent years, various UA derivatives have been synthesized through the transformation of numerous microbial strains. It is reported thatNocardia sp. NRRL 5646 converts UA into oleanolic acid methyl ester (Fig.5A ), in which two intermediates are formed by participation in the ”reverse biosynthesis” involving methyl migration from C-19 to C-20 57. A single component is produced by this biotransformation followed by hydrolysis to yield the corresponding triterpenoid acid. At the same time, UA has been found to be transformed into different derivatives by the same strain (Fig. 5B ). Researchers speculate that 3β-hydroxysteroid dehydrogenase and 3-ketosteroid-Δ1-dehydrogenase are involved in the transformation of steroid 58.