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A pair of residues that interactively affect diterpene synthase product outcome
Jia, Meirong1; Zhou, Ke1,2; Tufts, Samuel1; Schulte, Samuel1; Peters, Reuben J.1
刊名Acs chemical biology
2017-03-01
卷号12期号:3页码:862-867
ISSN号1554-8929
DOI10.1021/acschembio.6b01075
通讯作者Peters, reuben j.(rjpeters@iastate.edu)
英文摘要The labdane-related diterpenoids (lrds) are an important superfamily of natural products whose structural diversity critically depends on the hydrocarbon skeletal structures generated, in large part, by class i diterpene synthases. in the plant kingdom, where the lrds are predominantly found, the relevant class i diterpene synthases are clearly derived from the ent-kaurene synthase (ks) required in all land plants for phytohormone biosynthesis and, hence, are often termed ks-like (ksl). previous work, initiated by the distinct function of two alleles of a ksl from rice, osksls, identified a single residue switch with a profound effect on not only osksl5 product outcome but also that of land plant kss more broadly, specifically, replacement of a key isoleucine with threonine, which interrupts formation of the tetracyclic ent-isokaurene at the tricyclic stage, leading to production of ent-pimaradiene instead. here, further studies of these alleles led to discovery of another, nearby residue that tunes product outcome. substitution for this newly identified residue is additionally shown to exert an epistatic effect in kss, altering product distribution only if combined with replacement of the key isoleucine. on the other hand, this pair of residues was found to exert additive effects on the product outcome mediated by distantly related ksls from the eudicot castor bean. accordingly, it was possible to use a rational combination of substitutions for this pair of residues to engineer significantly increased (dominant) selectivity for novel 8 alpha-hydroxy-ent-pimar-15-ene product outcome in the ks from the dicot arabidopsis thaliana, demonstrating the utility of these results.
WOS关键词SPECIALIZED METABOLISM ; TERPENOID CYCLASES ; GENE FAMILY ; CATALYSIS ; BIOLOGY ; SWITCH
WOS研究方向Biochemistry & Molecular Biology
WOS类目Biochemistry & Molecular Biology
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000397077700031
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2176745
专题高能物理研究所
通讯作者Peters, Reuben J.
作者单位1.Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA
2.Chinese Acad Sci, Inst High Energy Phys, Multidisciplinary Res Ctr, Beijing 100049, Peoples R China
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GB/T 7714
Jia, Meirong,Zhou, Ke,Tufts, Samuel,et al. A pair of residues that interactively affect diterpene synthase product outcome[J]. Acs chemical biology,2017,12(3):862-867.
APA Jia, Meirong,Zhou, Ke,Tufts, Samuel,Schulte, Samuel,&Peters, Reuben J..(2017).A pair of residues that interactively affect diterpene synthase product outcome.Acs chemical biology,12(3),862-867.
MLA Jia, Meirong,et al."A pair of residues that interactively affect diterpene synthase product outcome".Acs chemical biology 12.3(2017):862-867.
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