Site-selective biotransformation of ursane triterpenes by Streptomyces griseus ATCC 13273

Abstract

The oxidization of unactivated C–H bonds of pentacyclic triterpenes (PTs) is of great interest for the structural modification of PTs.

Biotransformation of Oleanane and Ursane Triterpenic Acids

“…Substitutions of CYP88D6 (C11 oxidase) for Unigene25647 (97% similarity) and ATR1 (A. thaliana) for GuCPR1 (G. uralensis) were performed, and a combination of GuCPR1 and two Unigene25647 cassettes was inserted into the genome of S. cerevisiae SGib. These manipulations resulted in the formation of 18.9 ± 2.0 mg/L GA and about 80.0 mg/L 11-oxo-β-amyrin (15) after 144 h of the fed-batch fermentation with ethanol (30 mL every 24 h) compared with the previously obtained 20.4 ± 7.7 µg/L GA and 0.5 ± 0.1 mg/L 11-oxo-β-amyrin (15) and β-amyrin (6) and trace amounts of 11α-hydroxy-β-amyrin (16), 30-hydroxy-11-oxo-β-amyrin (17), and glycyrrhetaldehyde (18) [62]. In strain S. cerevisiae BY-OA, substitution of CYP716C49 (C. pinnatifida) for the homologue (47.9% similarity) CaCYP716C49 (C. asiatica) allowed for obtaining 384.3 mg/L maslinic acid (19, 2α-hydroxy-OA) after 96-h incubation in a 5-L fermenter with glucose (5 g/L).…”

“…griseus ATCC 13273 cells can also transform UA (0.04 g/L) by catalyzing site-selective oxidation of the C30 methyl group to the carboxyl one and C24-hydroxylation within 3 days to produce 3β-hydroxy-urs-12-ene-28,30-dioic acid ( 97 ) and 3β,24-dihydroxy-urs-12-ene-28,30-dioic acid ( 98 ), with the product yield exceeding 30.0%. Transformation of UA derivatives 3-oxo-UK ( 99 ) and 2α-hydroxy-UA ( 20 , corosolic acid) at a concentration of 0.04 g/L by this actinobacterial strain also occurred by selective C30-oxidation and hydroxylation, that led to a mixture of 3-oxo-urs-12-ene-28,30-dioic acid ( 100 , 24.1%) and 24-hydroxy-3-oxo-urs-12-ene-28,30-dioic acid ( 101 , 45.9%) in the former case and a mixture of 2α,3β-dihydroxy-urs-12-ene-28,30-dioic acid ( 102 , 29.0%) and 2α,3β,24-trihydroxy-urs-12-ene-28,30-dioic acid ( 103 , 15.9%) in the latter case [ 17 ].…”

“…Furthermore, microbial conversion ensures specific modifications of triterpenic molecule sites that are either not modified or poorly modified by synthetic transformations [ 12 ]. Note that, among the known microbial biocatalysts, members of mycelial fungi are the most studied [ 13 , 14 , 15 ] whereas bacterial catalysts are only represented by a few gram-positive species [ 16 , 17 , 18 , 19 , 20 ]. The first papers on microbial transformation of triterpenoids were published in the 1960s [ 21 ].…”

Biocatalysis of ursolic acid by the fungus Gliocladium roseum CGMCC 3.3657 and resulting anti-HCV activity

“…[10][11][12] Since UA does not have a lot of active sites for traditional organic modication, biocatalysis was investigated as a very good method to modify UA to obtain new metabolites. [13][14][15] The hepatitis C virus (HCV) infects 170 million people around the world and is mostly transmitted via parenteral routes. The increased risk of HCV development in HCV-infected patients arises from the development of liver brosis and cirrhosis as a result of chronic inammation.…”

Microbial synthesis of anti-tumor agent oxysophoridine through one step by filamentous fungus

“…Microbial transformation regarded as green, environment-friendly and sustainable has been increasing significantly in many fields. [14][15][16][17] There are many advantages on biotransformation, including mild conditions, less by-products and less contamination. The biotransformation reaction was usually operated at near neutral pH, ambient temperatures and atmospheric pressures.…”