Progress in Studying the Biosynthetic Mechanism of the Macrolide Immunosuppressant Tacrolimus

doi:10.6023/cjoc201212004

Chin. J. Org. Chem. ›› 2013, Vol. 33 ›› Issue (06): 1254-1262.DOI: 10.6023/cjoc201212004 Previous Articles Next Articles

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大环内酯类免疫抑制剂他克莫司的生物合成机制研究进展

陈单丹^a,b, 岑沛霖^a, 刘文^b, 徐志南^a

a 浙江大学化工系生物工程研究所杭州 310027;
b 中国科学院上海有机化学研究所生命有机国家重点实验室上海 200032

收稿日期:2012-12-05 修回日期:2013-01-06 发布日期:2013-01-11
通讯作者: 徐志南 E-mail:znxu@zju.edu.cn
基金资助:
国家自然科学基金(Nos.20832009, 21176214, 91213303);国家重点基础研究发展计划(973计划, Nos.2010CB833200, 2012CB721100).

Progress in Studying the Biosynthetic Mechanism of the Macrolide Immunosuppressant Tacrolimus

Chen Dandan^a,b, Cen Peilin^a, Liu Wen^b, Xu Zhinan^a

a Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027;
b State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032

Received:2012-12-05 Revised:2013-01-06 Published:2013-01-11
Supported by:
Project supported by the National Natural Science Foundation of China (Nos.20832009, 21176214, 91213303), the National Basic Research Program of China (973 Program, Nos.2010CB833200, 2012CB721100).

Tacrolimus (FK506), derived from various soil Streptomyces species, is a potent macrolide immunosuppressant that is assembled by a typical polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) hybrid system.Its chemical structure is unique, with a piperidine unit consisting in the polyketide skeleton, a 4-methoxy, 5-hydroxy-cyclohexyl functional group, as well as methoxyl and allyl side chains.Recently, studies on the biosynthetic mechanism of tacrolimus, particularly for the pathways encoding the unusual precursors, achieved great successes.In this review, we summarize the enzymatic basis in correspondence to the biosynthesis of tacrolimus, and emphasize on the recent progress in understanding the biosynthetic pathways of the unusual precursors 4,5-dihydroxycyclohex-1-enecarboxylic acid (DHCHC), methoxymalonyl-acyl carrier protein (ACP), allylmalonyl-coenzyme A (CoA) and L-pipecolic acid.

Key words: tacrolimus, FK506, biosynthesis, polyketide synthase (PKS), nonribosomal peptide synthetase (NRPS), precursor, pathway-specific

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Chen Dandan, Cen Peilin, Liu Wen, Xu Zhinan. Progress in Studying the Biosynthetic Mechanism of the Macrolide Immunosuppressant Tacrolimus[J]. Chin. J. Org. Chem., 2013, 33(06): 1254-1262.

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大环内酯类免疫抑制剂他克莫司的生物合成机制研究进展

Progress in Studying the Biosynthetic Mechanism of the Macrolide Immunosuppressant Tacrolimus

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