Production of human metabolites of cyclosporin A, AM1, AM4N and AM9, by microbial conversion

被引：9

作者：

Ohta, K ^{[1
]}

Agematu, H ^{[1
]}

Yamada, T ^{[1
]}

Kaneko, K ^{[1
]}

Tsuchida, T ^{[1
]}

机构：

[1] Mercian Corp, Bioresource Labs, Shizuoka 4380078, Japan

来源：

JOURNAL OF BIOSCIENCE AND BIOENGINEERING | 2005年 / 99卷 / 04期

关键词：

cyclosporin A; AM1; AM4N; AM9; microbial conversion; bioconversion; cytochrome P450;

D O I：

10.1263/jbb.99.390

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

In humans, cyclosporin A (CyA) is primarily metabolized to two hydroxylated (AM1 and AM9) and one N-demethylated (AM4N) derivative. To produce these derivatives, 1237 actinomycetes were screened for their ability to convert CyA. Among them, 89 strains (7.2%) produced these derivatives from CyA. Finally, Dactylosporangium variesporum IFO 14104, Actinoplanes sp. ATCC 53771 and Streptosporangium sp. AF935 were selected for the production of AM1, AM4N, and AM9, respectively. Composition of the production medium and the incubation period with CyA were important for obtaining a high yield of CyA derivatives. Large-scale microbial conversion of CyA (1.5 g) using a 30-l jar fermentor yielded 288 mg of AM1 (19.2%), 147 mg of AM4N (9.8%) and 115 mg of AM9 (7.7%).

引用

页码：390 / 395

页数：6

共 23 条

[1] Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2) [J].

Bentley, SD ;

Chater, KF ;

Cerdeño-Tárraga, AM ;

Challis, GL ;

Thomson, NR ;

James, KD ;

Harris, DE ;

Quail, MA ;

Kieser, H ;

Harper, D ;

Bateman, A ;

Brown, S ;

Chandra, G ;

Chen, CW ;

Collins, M ;

Cronin, A ;

Fraser, A ;

Goble, A ;

Hidalgo, J ;

Hornsby, T ;

Howarth, S ;

Huang, CH ;

Kieser, T ;

Larke, L ;

Murphy, L ;

Oliver, K ;

O'Neil, S ;

Rabbinowitsch, E ;

Rajandream, MA ;

Rutherford, K ;

Rutter, S ;

Seeger, K ;

Saunders, D ;

Sharp, S ;

Squares, R ;

Squares, S ;

Taylor, K ;

Warren, T ;

Wietzorrek, A ;

Woodward, J ;

Barrell, BG ;

Parkhill, J ;

Hopwood, DA .

NATURE, 2002, 417 (6885) :141-147

[2] MICROBIAL HYDROXYLATION AND GLUCURONIDATION OF THE ANGIOTENSIN-II (AII) RECEPTOR ANTAGONIST MK-954 [J].

CHEN, TS ;

SO, L ;

WHITE, R ;

MONAGHAN, RL .

JOURNAL OF ANTIBIOTICS, 1993, 46 (01) :131-134

[3] MICROBIAL TRANSFORMATION OF IMMUNOSUPPRESSIVE COMPOUNDS .1. DESMETHYLATION OF FK506 AND IMMUNOMYCIN (FR-900520) BY ACTINOPLANES SP ATCC-53771 [J].

CHEN, TS ;

ARISON, BH ;

WICKER, LS ;

INAMINE, ES ;

MONAGHAN, RL .

JOURNAL OF ANTIBIOTICS, 1992, 45 (01) :118-123

[4] MICROBIAL TRANSFORMATION OF L-696,474, A NOVEL CYTOCHALASIN AS AN INHIBITOR OF HIV-1 PROTEASE [J].

CHEN, TS ;

DOSS, GA ;

HSU, A ;

LINGHAM, RB ;

WHITE, RF ;

MONAGHAN, RL .

JOURNAL OF NATURAL PRODUCTS, 1993, 56 (05) :755-761

[5] INVESTIGATIONS ON THE METABOLIC PATHWAYS OF CYCLOSPORINE .2. ELUCIDATION OF THE METABOLIC PATHWAYS INVITRO BY HUMAN LIVER-MICROSOMES [J].

CHRISTIANS, U ;

STROHMEYER, S ;

KOWNATZKI, R ;

SCHIEBEL, HM ;

BLECK, J ;

KOHLHAW, K ;

SCHOTTMANN, R ;

SEWING, KF .

XENOBIOTICA, 1991, 21 (09) :1199-1210

[6] SYNTHESIS OF THE MAIN METABOLITE (OL-17) OF CYCLOSPORIN-A [J].

EBERLE, MK ;

NUNINGER, F .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (09) :2689-2691

[7] Microbial conversion of EM574 and EM523, gastrointestinal motor stimulating agents [J].

Funabashi, Y ;

Hakoda, S ;

Inatomi, N ;

Koyama, K ;

Tanida, S ;

Harada, S ;

Itoh, Z ;

Omura, S .

JOURNAL OF ANTIBIOTICS, 1996, 49 (08) :802-810

[8]

Gotoh O., 1993, CYTOCHROME P450, P255

[9] Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis [J].

Ikeda, H ;

Ishikawa, J ;

Hanamoto, A ;

Shinose, M ;

Kikuchi, H ;

Shiba, T ;

Sakaki, Y ;

Hattori, M ;

Omura, S .

NATURE BIOTECHNOLOGY, 2003, 21 (05) :526-531

[10] PEPTIDE CONFORMATIONS .30. ASSIGNMENT OF THE H-1-NMR, C-13-NMR, AND N-15-NMR SPECTRA OF CYCLOSPORIN-A IN CDCL3 AND C6D6 BY A COMBINATION OF HOMONUCLEAR AND HETERONUCLEAR TWO-DIMENSIONAL TECHNIQUES [J].

KESSLER, H ;

LOOSLI, HR ;

OSCHKINAT, H .

HELVETICA CHIMICA ACTA, 1985, 68 (03) :661-681

← 1 2 3 →