Deciphering the Biosynthetic Origin of L-allo-Isoleucine
文献类型：期刊论文
| 作者 | Li, Qinglian; Qin, Xiangjing; Liu, Jing; Gui, Chun; Wang, Bo; Li, Jie; Ju, Jianhua |
| 刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
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| 出版日期 | 2016 |
| 卷号 | 138期号:1页码:408-415 |
| 通讯作者 | Ju, JH (reprint author), Chinese Acad Sci, South China Sea Inst Oceanol, Ctr Marine Microbiol, CAS Key Lab Trop Marine Bioresources & Ecol,RNAM, Guangzhou 510301, Guangdong, Peoples R China. |
| 中文摘要 | The nonproteinogenic amino acid L-allo-isoleucine (L-allo-Ile) is featured in an assortment of life forms comprised of, but not limited to, bacteria, fungi, plants and mammalian systems including Homo sapiens. Despite its ubiquity and functional importance, the specific origins of this unique amino acid have eluded characterization. In this study, we describe the discovery and characterization of two enzyme pairs consisting of a pyridoxal 5'-phosphate (PLP)-linked aminotransferase and an unprecedented isomerase synergistically responsible for the biosynthesis of L-allo-Ile from L-isoleucine (L-Ile) in natural products. DsaD/DsaE from the desotamide biosynthetic pathway in Streptomyces scopuliridis SCSIO ZJ46, and MfnO/MfnH from the marformycin biosynthetic pathway in Streptomyces drozdowiczii SCSIO 10141 drive L-allo-Ile generation in each respective system. In vivo gene inactivations validated the importance of the DsaD/DsaE pair and MfnO/MfnH pair in L-allo-Ile unit biosynthesis. Inactivation of PLP-linked aminotransferases DsaD and MfnO led to significantly diminished desotamide and marformycin titers, respectively. Additionally, inactivation of the isomerase genes dsaE and mfnH completely abolished production of all containing metabolites in both biosynthetic pathways. Notably, in vitro biochemical assays revealed that DsaD/DsaE and MfnO/MfnH each catalyze a bidirectional reaction between L-allo-Ile and Site-directed mutagenesis experiments revealed that the enzymatic reaction involves a PLP-linked ketimine intermediate and uses an arginine residue from the C-terminus of each isomerase to epimerize the amino acid beta-position. Consequently, these data provide important new insight into the origins of Lallo-Ile in natural products with medicinal potential and illuminate new possibilities for biotool development. |
| 学科主题 | Chemistry |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/15511]  |
| 专题 | 南海海洋研究所_中科院海洋生物资源可持续利用重点实验室 |
| 推荐引用方式 GB/T 7714 | Li, Qinglian,Qin, Xiangjing,Liu, Jing,et al. Deciphering the Biosynthetic Origin of L-allo-Isoleucine[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2016,138(1):408-415. |
| APA | Li, Qinglian.,Qin, Xiangjing.,Liu, Jing.,Gui, Chun.,Wang, Bo.,...&Ju, Jianhua.(2016).Deciphering the Biosynthetic Origin of L-allo-Isoleucine.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,138(1),408-415. |
| MLA | Li, Qinglian,et al."Deciphering the Biosynthetic Origin of L-allo-Isoleucine".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 138.1(2016):408-415. |
入库方式： OAI收割
来源：南海海洋研究所
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