在7月的Chemistry and Biology雜志上,，來自威斯康星州大學的華人學者高群杰、張常勝等人公布了有關通過比較基因組學方法來破譯吲哚咔唑(indolocarbazole)和Enediyne Aminodideoxypentose生物合成的文章,。
AT2433是一種吲哚咔唑抗腫瘤藥物，其結構的獨特性在于它的具有含aminodideoxypentose的二糖（disaccharide）和不對稱的鹵化N-methylated aglycon,。利用比較基因組學方法,，對AT2433基因束的克隆和測序分析并對這種基因座與編碼rebeccamycin和calicheamicin進行比較能夠研究aminodideoxypentose的生物合成。
這種基因座兩種甲基轉移酶的離體生化特征以及利用AT2433 N-glycosyltransferase進行雜交表達和活體生物轉化實驗所確證,。其中一種甲基化酶能修飾AT2433和蝴蝶霉素(Rebeccamycin),；另外一種酶則對AT2433具有特異性。
對底物對這三種酶的耐受性分析的初步結果表明有可能擴展indolacarbazoles的酶多樣性,。而且,，這項研究也為進一步研究indolocarbazole maleimide nitrogen和indolocarbazole的不對稱性奠定了基礎。
部分英文原文：
Deciphering Indolocarbazole and Enediyne Aminodideoxypentose Biosynthesis through Comparative Genomics: Insights from the AT2433 Biosynthetic Locus
AT2433, an indolocarbazole antitumor antibiotic, is structurally distinguished by its aminodideoxypentose-containing disaccharide and asymmetrically halogenated N-methylated aglycon. Cloning and sequence analysis of AT2433 gene cluster and comparison of this locus with that encoding for rebeccamycin and the gene cluster encoding calicheamicin present an opportunity to study the aminodideoxypentose biosynthesis via comparative genomics. The locus was confirmed via in vitro biochemical characterization of two methyltransferases-one common to AT2433 and rebeccamycin, the other unique to AT2433-as well as via heterologous expression and in vivo bioconversion experiments using the AT2433 N-glycosyltransferase. Preliminary studies of substrate tolerance for these three enzymes reveal the potential to expand upon the enzymatic diversification of indolocarbazoles. Moreover, this work sets the stage for future studies regarding the origins of the indolocarbazole maleimide nitrogen and indolocarbazole asymmetry.
