Biocatalysis of Cycloastragenol by Syncephalastrum racemosum and Alternaria alternata to Discover Anti-Aging Derivatives

Cycloastragenol is a cycloartane-type triterpenoid with significant telomerase-activating activities. In this paper, the biocatalysis of cycloastragenol by two strains of filamentous fungi, namely Syncephalastrum racemosum AS 3.264 and Alternaria alternata AS 3.4578, was investigated. Scaled-up biotransformation reactions yielded 27 metabolites. Their structures were established on the basis of extensive NMR and HR-ESI-MS data analyses, and 18 of them are new compounds. The two fungal strains exhibited distinct biocatalytic features. S. racemosum could catalyze ring expansion and epoxidation reactions to form 3 beta,10 beta-epoxy- or 6 alpha,19 alpha-epoxy-9,10-seco-cycloartane structures, whereas A. alternata preferred to catalyze acetylation reactions, especially at 3-OH, 6-OH and 19-OH. These regio- and stereoselective reactions are difficult to achieve by chemical means, but could be realized under mild conditions by biocatalysis. Furthermore, we found that some acetylated derivatives at 50 mu M could significantly extend the lifespan of Caenorhabditis elegans from 16.93 +/- 0.70 d of the control group to 20.01 +/- 0.75 d (P<0.01), versus 18.54 +/- 0.67 d for cycloastragenol. These biotransformed derivatives of cycloastragenol could be potential anti-aging agents.