Microbial transformation of cephalomannine by Luteibacter sp.
Luteibacter sp., a new bacterium isolated from the soil around a Taxus cuspidata Sieb. et Zucc plant, was studied for its capability to metabolize cephalomannine (1). After preparative fermentation, eight metabolites were obtained and characterized as baccatin III (2), baccatin V (3), 10-deacetylbaccatin III (4), 10-deacetyl-10-oxobaccatin V (5), 7-epicephalomannine (6), 10-deacetylcephalomannine (7), 10-deacetyl-7-epicephalomannine (8), and 3'-N-debenzoyl-3'-N-(2-methylbutyryl)-7-epitaxol (9). Among these metabolites, 9 is a new compound. Epimerization of the 7beta-OH group and hydrolysis of the C-13 side-chain were the two major reactions in this bioprocess. However, the biotransformation of 7beta-D-xylosyl-10-deacetyltaxol (10) with the same strain yielded a C-13 side-chain eliminated product without epimerization at C-7 (11). Metabolites 5-9 and 11, together with 1 and paclitaxel, were evaluated for their inhibitory activities against five human cancer cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780). All these compounds showed less potent activities than paclitaxel, which is currently used in clinical chemotherapy.
Li
Jianhua
J
Department of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Dai
Jungui
J
Chen
Xiaoguang
X
Zhu
Ping
P
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001419:Bacteria / Q000302:isolation & purification* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D012988:Soil Microbiology; D043823:Taxoids / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D020946:Taxus
D000470:Alkaloids; D000970:Antineoplastic Agents; D043823:Taxoids; C073950:baccatin III; C042213:10-deacetylbaccatine III; C056348:cephalomannine; D017239:Paclitaxel