Discovery of a pathway for terminal-alkyne amino acid biosynthesis
Discovery of a pathway for terminal-alkyne amino acid biosynthesis
复制标题
DOI：
10.1038/s41586-019-1020-y
复制
发表时间：
2019-03-21
期刊：
影响因子：
64.8
通讯作者：
Chang, M. C. Y.
中科院分区：
文献类型：
--
作者：
Marchand, J. A.;Neugebauer, M. E.;Chang, M. C. Y.
生命系统可以产生大量的细胞功能，从机械基础设施和信号网络到酶催化和信息存储，使用一组非常有限的化学官能团。当与用作合成衍生的小分子和材料中类似功能的基础的官能团的宽度相比时，该观察结果尤其显著。生物和合成反应空间之间相对较小的横截面形成了生物正交化学发展的基础，其中细胞内不存在一对反应性官能团允许选择性原位反应（1-4）。然而，在植物、真菌和微生物制造的天然产物中继续发现生物学上“稀有”的官能团，例如氟（5）、氯（6，7）、溴（7，8）、膦酸酯（9）、烯二炔（10，11）、氰基（12）、重氮（13）、烯烃（14）和炔（15-17）基团，其提供了在活生物体内遗传编码生物正交试剂的内源性生物合成的潜在途径。特别地，已经发现末端炔经Cu（I）催化的叠氮化物-炔环加成“点击”反应的广泛用途（18）。在这里，我们报告了一个独特的途径，以产生一个末端含炔的氨基酸在细菌链霉菌卡特兰的发现和表征。我们发现，L-赖氨酸经历了一个意想不到的反应序列，包括卤化，氧化C-C键断裂和三键形成通过一个假定的丙二烯中间体。这种途径提供了从头细胞生产的卤素，烯烃和炔烃标记的蛋白质和天然产物从葡萄糖的各种下游应用的潜力。
Living systems can generate an enormous range of cellular functions, from mechanical infrastructure and signalling networks to enzymatic catalysis and information storage, using a notably limited set of chemical functional groups. This observation is especially notable when compared to the breadth of functional groups used as the basis for similar functions in synthetically derived small molecules and materials. The relatively small cross-section between biological and synthetic reactivity space forms the foundation for the development of bioorthogonal chemistry, in which the absence of a pair of reactive functional groups within the cell allows for a selective in situ reaction(1-4). However, biologically 'rare' functional groups, such as the fluoro(5), chloro(6,7), bromo(7,8), phosphonate(9), enediyne(10,11), cyano(12,) diazo(13), alkene(14) and alkyne(15-17) groups, continue to be discovered in natural products made by plants, fungi and microorganisms, which offers a potential route to genetically encode the endogenous biosynthesis of bioorthogonal reagents within living organisms. In particular, the terminal alkyne has found broad utility via the Cu(i)-catalysed azide-alkyne cycloaddition 'click' reaction(18). Here we report the discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya. We found that l-lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C-C bond cleavage and triple bond formation through a putative allene intermediate. This pathway offers the potential for de novo cellular production of halo-, alkene-and alkyne-labelled proteins and natural products from glucose for a variety of downstream applications.