Constructing de novo biosynthetic pathways for chemical synthesis inside living cells.
Constructing de novo biosynthetic pathways for chemical synthesis inside living cells.
复制标题
构建从头生物合成途径，用于活细胞内化学合成。
DOI：
10.1021/bi200416g
复制
发表时间：
2011-06-21
期刊：
影响因子：
2.9
通讯作者：
Chang, Michelle C. Y.
中科院分区：
文献类型：
--
作者：
Weeks, Amy M.;Chang, Michelle C. Y.
生物体已经进化出大量的催化功能，使它们非常适合于生产医学和工业相关的小分子靶标。事实上，微生物宿主中的天然代谢途径长期以来一直被开发和优化，用于精细化学品和商品化学品的规模化生产。我们不断提高的DNA测序和合成能力揭示了各种复杂和有用的代谢物生物合成的分子基础，并使从头构建新的代谢途径，用于在遗传上易处理的微生物中产生新的和外来的分子靶标。然而，这些工程化途径的商业上可行的方法的开发目前受到我们快速鉴定或工程化具有正确反应和底物选择性的酶的能力以及确定和校正代谢瓶颈的速度的限制。在理解基础生物化学科学中序列、结构和功能之间的关系方面所做的努力可以推进合成生物学应用的这些目标，同时也可以作为一个实验平台来阐明酶的体内特异性和功能，并重建复杂的生物化学特性，以供在活的模式生物中进行研究。此外，对调节代谢途径的天然机制的不断发现揭示了设计具有最小化代谢负担的高通量途径的新原则，并激发了开发新工具和方法来设计微生物宿主中的合成途径以用于化学生产。
Living organisms have evolved a vast array of catalytic functions that make them ideally suited for the production of medicinally and industrially relevant small-molecule targets. Indeed, native metabolic pathways in microbial hosts have long been exploited and optimized for the scalable production of both fine and commodity chemicals. Our increasing capacity for DNA sequencing and synthesis has revealed the molecular basis for the biosynthesis of a variety of complex and useful metabolites and enables the de novo construction of novel metabolic pathways for the production of new and exotic molecular targets in genetically tractable microbes. However, the development of commercially viable processes for these engineered pathways is currently limited by our ability to quickly identify or engineer enzymes with the correct reaction and substrate selectivity as well as the speed by which metabolic bottlenecks can be determined and corrected. Efforts in understanding the relationship between sequence, structure, and function in the basic biochemical sciences can advance these goals for synthetic biology applications while also serving as an experimental platform to elucidate the in vivo specificity and function of enzymes and to reconstitute complex biochemical traits for study in a living model organism. Furthermore, the continuing discovery of natural mechanisms for the regulation of metabolic pathways has revealed new principles for the design of high-flux pathways with minimized metabolic burden and has inspired the development of new tools and approaches to engineer synthetic pathways in microbial hosts for chemical production.
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影响因子：
5.6
作者：
Bershtein, Shimon;Goldin, Korina;Tawfik, Dan S.
通讯作者：
Tawfik, Dan S.
ORM家族蛋白介导鞘脂稳态。
影响因子：
64.8
作者：
Breslow, David K.;Collins, Sean R.;Bodenmiller, Bernd;Aebersold, Ruedi;Simons, Kai;Shevchenko, Andrej;Ejsing, Christer S.;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.
DOI：
10.1073/pnas.74.2.492
发表时间：
1977-01-01
影响因子：
11.1
作者：
BINSTOCK, JF;PRAMANIK, A;SCHULZ, H
通讯作者：
SCHULZ, H
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
8.4
作者：
Anthony, Jennifer R.;Anthony, Larry C.;Keasling, Jay D.
通讯作者：
Keasling, Jay D.