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Deciphering the Biosynthetic Origin of L-allo-Isoleucine
Li, Qinglian; Qin, Xiangjing; Liu, Jing; Gui, Chun; Wang, Bo; Li, Jie; Ju, Jianhua; 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.
2016
Source PublicationJOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume138Issue:1Pages:408-415
AbstractThe 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.
Department[Li, Qinglian; Qin, Xiangjing; Liu, Jing; Gui, Chun; Wang, Bo; Li, Jie; Ju, Jianhua] 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 ; LMB
Subject AreaChemistry
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/15511
Collection中科院海洋生物资源可持续利用重点实验室
Corresponding AuthorJu, 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.
Recommended Citation
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, JH .(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.
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