A biosynthetic pathway for BE-7585A, a 2-thiosugar-containing angucycline-type natural product.
A biosynthetic pathway for BE-7585A, a 2-thiosugar-containing angucycline-type natural product.
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DOI：
10.1021/ja1014037
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发表时间：
2010-06-02
影响因子：
15
通讯作者：
Liu, Hung-wen
中科院分区：
文献类型：
--
作者：
Sasaki, Eita;Ogasawara, Yasushi;Liu, Hung-wen
硫是生命系统中普遍存在的一种基本元素。然而，自然界中只存在少量的含硫糖，其生物合成还没有得到研究。东方无枝霉产生BE-7585A。Venearia BA-07585具有2-硫代糖，是绞股蓝环素类化合物的成员。我们在此报告了我们研究BE-7585A生物合成的初步努力的结果。光谱分析证实了BE-7585A的结构，它与红景天素A密切相关。用13C标记的醋酸酯进行喂食实验，证实了安古环素核心确实是聚酮衍生的。结果表明，可能是通过Baeyer-Villiger类型的重排，以一种不寻常的方式构建了角四环。随后的克隆和测序导致了跨度约30kbp的Bex基因簇的鉴定。在该簇中发现了28个可能参与BE-7585A形成的开放阅读框。鉴于Bex簇中存在噻唑合成酶基因(Thig)的同源基因Bexx，硫结合到2-硫糖部分的机制可能类似于硫胺素生物合成中的机制。在大肠杆菌中异源表达了糖基转移酶同源物BexG2。纯化的酶成功催化6-磷酸-2-硫代葡萄糖和UDP-葡萄糖偶联生成BE-7585A双糖单元的前体--2-硫代海藻糖-6-磷酸。在这些遗传和生化实验的基础上，现在可以提出BE-7585A的生物合成途径。综合结果为未来2-硫糖生物合成和BE-7585A组装的生化研究奠定了基础。
Sulfur is an essential element found ubiquitously in living systems. However, there exist only a few sulfur-containing sugars in nature and their biosyntheses have not been studied. BE-7585A produced by Amycolatopsis orientalis subsp. vinearia BA-07585 has a 2-thiosugar and is a member of the angucycline class of compounds. We report herein the results of our initial efforts to study the biosynthesis of BE-7585A. Spectroscopic analyses verified the structure of BE-7585A, which is closely related to rhodonocardin A. Feeding experiments using 13C-labeled acetate were carried out to confirm that the angucycline core is indeed polyketide-derived. The results indicated an unusual manner of angular tetracyclic ring construction, perhaps via a Baeyer-Villiger type rearrangement. Subsequent cloning and sequencing led to the identification of the bex gene cluster spanning ~30 kbp. A total of 28 open reading frames, which are likely involved in BE-7585A formation, were identified in the cluster. In view of the presence of a homologue of a thiazole synthase gene (thiG), bexX, in the bex cluster, the mechanism of sulfur incorporation into the 2-thiosugar moiety could resemble that found in thiamin biosynthesis. A glycosyltransferase homologue, BexG2, was heterologously expressed in E. coli. The purified enzyme successfully catalyzed the coupling of 2-thioglucose 6-phoshate and UDP-glucose to produce 2-thiotrehalose 6-phosphate, which is the precursor of the disaccharide unit in BE-7585A. On the basis of these genetic and biochemical experiments, a biosynthetic pathway for BE-7585A can now be proposed. The combined results set the stage for future biochemical studies of 2-thiosugar biosynthesis and BE-7585A assembly.
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影响因子：
15
作者：
Chen, HW;Agnihotri, G;Liu, HW
通讯作者：
Liu, HW
影响因子：
3.4
作者：
Avonce N;Mendoza-Vargas A;Morett E;Iturriaga G
通讯作者：
Iturriaga G
DOI：
10.1099/00221287-146-1-147
发表时间：
2000-01-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Faust, B;Hoffmeister, D;Bechthold, A
通讯作者：
Bechthold, A
影响因子：
3.5
作者：
BIERMAN, M;LOGAN, R;SCHONER, BE
通讯作者：
SCHONER, BE
影响因子：
3.6
作者：
GOULD, SJ;CHENG, XC
通讯作者：
CHENG, XC