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Chinese Journal of Organic Chemistry >

2013 , Vol. 33 >Issue 06: 1254 - 1262

DOI: https://doi.org/10.6023/cjoc201212004

Reviews

Progress in Studying the Biosynthetic Mechanism of the Macrolide Immunosuppressant Tacrolimus

  • Chen Dandan ,
  • Cen Peilin ,
  • Liu Wen ,
  • Xu Zhinan
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  • 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 date: 2012-12-05

  Revised date: 2013-01-06

  Online 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).

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Abstract

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

Cite this article

Chen Dandan , Cen Peilin , Liu Wen , Xu Zhinan . Progress in Studying the Biosynthetic Mechanism of the Macrolide Immunosuppressant Tacrolimus[J]. Chinese Journal of Organic Chemistry, 2013 , 33(06) : 1254 -1262 . DOI: 10.6023/cjoc201212004

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