Large-scale isolation and crystallization of epothilone D from Myxococcus xanthus cultures

被引:26
作者
Arslanian, RL [1 ]
Parker, CD [1 ]
Wang, PK [1 ]
McIntire, JR [1 ]
Lau, J [1 ]
Starks, C [1 ]
Licari, PJ [1 ]
机构
[1] Kosan Biosci Inc, Hayward, CA 94545 USA
来源
JOURNAL OF NATURAL PRODUCTS | 2002年 / 65卷 / 04期
关键词
D O I
10.1021/np010438s
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
The introduction of the epothilone polyketide synthase (PKS) into Myxococcus xanthus has enabled the heterologous production of epothilone D (1) on a large scale. To isolate this valuable product from the fermentation medium, an economical, scalable, and high-yielding purification process was developed. With the crystallization of I from a binary solvent system that consisted of ethanol and water, the product was recovered as white crystals with a final purity of greater than or equal to97% (w/w). This is the first reported crystallization of 1.
引用
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页码:570 / 572
页数:3
相关论文
共 15 条
[1]  
BOLLAG DM, 1995, CANCER RES, V55, P2325
[2]   Desoxyepothilone B:: An efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone B [J].
Chou, TC ;
Zhang, XG ;
Balog, A ;
Su, DS ;
Meng, DF ;
Savin, K ;
Bertino, JR ;
Danishefsky, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (16) :9642-9647
[3]   Epothilons A and B: Antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria) - Production, physico-chemical and biological properties [J].
Gerth, K ;
Bedorf, N ;
Hofle, G ;
Irschik, H ;
Reichenbach, H .
JOURNAL OF ANTIBIOTICS, 1996, 49 (06) :560-563
[4]   Studies on the biosynthesis of epothilones:: The PKS and epothilone C/D monooxygenase [J].
Gerth, K ;
Steinmetz, H ;
Höfle, G ;
Reichenbach, H .
JOURNAL OF ANTIBIOTICS, 2001, 54 (02) :144-148
[5]   New natural epothilones from Sorangium cellulosum, strains So ce90/B2 and So ce90/D13:: Isolation, structure elucidation, and SAR studies [J].
Hardt, IH ;
Steinmetz, H ;
Gerth, K ;
Sasse, F ;
Reichenbach, H ;
Höfle, G .
JOURNAL OF NATURAL PRODUCTS, 2001, 64 (07) :847-856
[6]   New chemical synthesis of the promising cancer chemotherapeutic agent 12,13-desoxyepothilone B: Discovery of a surprising long-range effect on the diastereoselectivity of an aldol condensation [J].
Harris, CR ;
Kuduk, SD ;
Balog, A ;
Savin, K ;
Glunz, PW ;
Danishefsky, SJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (30) :7050-7062
[7]  
HOFFMAN H, 2001, Patent No. 6194181
[8]   Epothilone A and B - Novel 16-membered macrolides with cytotoxic activity: Isolation, crystal structure, and conformation in solution [J].
Hofle, GH ;
Bedorf, N ;
Steinmetz, H ;
Schomburg, D ;
Gerth, K ;
Reichenbach, H .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1996, 35 (13-14) :1567-1569
[9]   Synthesis, structure proof, and biological activity of epothilone cyclopropanes [J].
Johnson, J ;
Kim, SH ;
Bifano, M ;
DiMarco, J ;
Fairchild, C ;
Gougoutas, J ;
Lee, F ;
Long, B ;
Tokarski, J ;
Vite, G .
ORGANIC LETTERS, 2000, 2 (11) :1537-1540
[10]  
JULIEN B, UNPUB P NATL ACAD SC