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The outer edges of the Lzr gene cluster were defined based on comparisons to the BE-54017 and cladoniamide gene clusters and a BLAST analysis of genes surrounding the core indolotryptoline biosynthesis genes (Fig. 3A). The biosynthesis of indolotryptolines is well-character- ized, making it possible to predict the function of most genes in the Lzr gene cluster (32). The four key stages of indolotryptoline biosynthesis involve dimerization of oxo-tryptophan to form a chromopyrrolic acid, oxidative aryl–aryl coupling to form an indolocarbazole, “flipping” of one of the indole rings to form an indolotryptoline, and tailoring to generate the final product. The Lzr gene cluster is predicted to contain seven transcriptional units controlled by three bidirectional (P1, P2, and P3) and one unidirectional (P4) promoter regions (Fig. 3 B, i). This cluster is conveniently organized such that successive activation of the three bidirectional promoter regions (P1, P2, and P3) is predicted to drive the expression of genes required to achieve the first, second, and third stages in indolotryptoline biosynthesis, respectively (Fig. 3C). |
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| 基于對(duì)BE-54017以及cladoniamide基因簇的比較,以及吲哚色氨酸周?chē)蛏锖铣傻腂LAST分析(圖3A),我們定義了Lzr基因簇的范圍。吲哚色氨酸的生物合成是人們所熟知的,這使得預(yù)測(cè)Lzr基因簇中的基團(tuán)功能成為可能。吲哚色氨酸的四個(gè)關(guān)鍵合成步驟包括1.氧雜色氨酸形成吡咯酸,2. 氧化芳基-芳基偶聯(lián)生成吲哚咔唑, 3. 吲哚環(huán)的骨架遷躍生成吲哚色氨酸琳,4. 形成終產(chǎn)物。Lzr基因簇含有七個(gè)轉(zhuǎn)錄單元,由三個(gè)雙向啟動(dòng)區(qū)P1 P2 P3以及一個(gè)單向啟動(dòng)區(qū)P4控制 。這種有序的組織使得連續(xù)活化 三個(gè)雙向啟動(dòng)區(qū)(P1 P2 P3)成為一種驅(qū)動(dòng)力,分別實(shí)現(xiàn)吲哚色氨酸的三個(gè)階段性合成 |

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