Opportunities in metabolic engineering to facilitate scalable alkaloid production
Opportunities in metabolic engineering to facilitate scalable alkaloid production
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DOI：
10.1038/nchembio.160
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发表时间：
2009-05-01
影响因子：
14.8
通讯作者：
Prather, Kristala Jones
中科院分区：
文献类型：
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作者：
Leonard, Effendi;Runguphan, Weerawat;Prather, Kristala Jones
c现行药典中的许多药物和药物前体来源于植物。然而，植物组织中某些生物活性化合物的产量有限，这对大规模药物开发提出了重大挑战。代谢工程促进了植物细胞和组织系统的发展，作为可在受控环境中扩大规模的替代生产平台。然而，有效的代谢工程方法和遗传转化的可预测性往往是模糊的，由于无数的细胞复杂性。系统生物学的进展有助于理解植物系统中的全基因组互连性。与此同时，微生物中植物生物合成途径的自下而上的组装展示了新生产手段的可能性。在这个角度来看，我们讨论的机遇和挑战，实施代谢工程在各种平台的天然和非天然植物生物碱的合成。
cNumerous drugs and drug precursors in the current pharmacopoeia originate from plant sources. The limited yield of some bioactive compounds in plant tissues, however, presents a significant challenge for large-scale drug development. Metabolic engineering has facilitated the development of plant cell and tissue systems as alternative production platforms that can be scaled up in a controlled environment. Nevertheless, effective metabolic engineering approaches and the predictability of genetic transformations are often obscured due to the myriad cellular complexities. Progress in systems biology has aided the understanding of genome-wide interconnectivities in plant-based systems. In parallel, the bottom-up assembly of plant biosynthetic pathways in microorganisms demonstrated the possibilities of a new means of production. In this Perspective, we discuss the opportunities and challenges of implementing metabolic engineering in various platforms for the synthesis of natural and unnatural plant alkaloids.