Microbial transformations of betulinic and betulonic acids

Animesh Goswami, Zhiwei Guo, Thomas P. Tully, Frank A. Rinaldi, Xiaohua Stella Huang, Jacob J. Swidorski, Alicia Regueiro-Ren

Abstract

Enzymatic transformation of betulinic acid by growing cells of microorganisms provided several hydroxylated and oxidized products. Bacillus megaterium SC16644 gave 7β,15α-dihydroxybetulinic acid, 7β,15α-dihydroxybetulonic acid, and a new compound 7β,15α,23-trihydroxybetulinic acid [3β,7β,15α,23-tetrahydroxy-lup-20(29)en-28-oic acid]. Another strain of B. megaterium SC6394 produced 30-oxobetulonic acid, and a mixture of 30-hydroxybetulonic acid and a new compound 7β-hydroxy-30-oxobetulonic acid [7β-hydroxy-3,30-dioxo-lup-20(29)en-28-oic acid]. Three products were obtained from the biotransformation of betulinic acid by Streptomyces fragilis SC16401: 7β-hydroxybetulonic acid, and two new compounds 2α,7β-dihydroxybetulinic acid [2α,3β,7β-trihydroxy-lup-20(29)en-28-oic acid] and 2-oxo-7β-hydroxy-betulinic acid [2-oxo-3β,7β-dihydroxy-lup-20(29)en-28-oic acid]. Cunninghamella elegans SC16025 gave 25-hydroxybetulinic acid from betulinic acid. Oxidation of betulinic acid by Aspergillus terreus SC16513 led to two A-ring fission products: 4-hydroxy-3,4-seco-lup-20(29)-en-3,28-dioic acid and 3,4-seco-lup-20(29), 4(23)-dien-3,28-dioic acid. B. megaterium SC16644 catalyzed transformation of betulonic acid provided 7β-hydroxybetulonic acid, 7β,15α-dihydroxybetulonic acid, and a new compound 7β,15α,30-trihydroxybetulonic acid [3-oxo-7β,15α,30-trihydroxy-lup-20(29)en-28-oic acid].

Graphical abstract

Keywords: Betulinic acid; Betulonic acid; Microbial transformation; Enzymatic hydroxylation; Enzymatic oxidation.