Chang Michelle C Y, Keasling Jay D
California Institute for Quantitative Biomedical Research, University of California-Berkeley, Berkeley, CA 94720, USA.
Nat Chem Biol. 2006 Dec;2(12):674-81. doi: 10.1038/nchembio836.
Throughout human history, natural products have been the foundation for the discovery and development of therapeutics used to treat diseases ranging from cardiovascular disease to cancer. Their chemical diversity and complexity have provided structural scaffolds for small-molecule drugs and have consistently served as inspiration for medicinal design. However, the chemical complexity of natural products also presents one of the main roadblocks for production of these pharmaceuticals on an industrial scale. Chemical synthesis of natural products is often difficult and expensive, and isolation from their natural sources is also typically low yielding. Synthetic biology and metabolic engineering offer an alternative approach that is becoming more accessible as the tools for engineering microbes are further developed. By reconstructing heterologous metabolic pathways in genetically tractable host organisms, complex natural products can be produced from inexpensive sugar starting materials through large-scale fermentation processes. In this Perspective, we discuss ongoing research aimed toward the production of terpenoid natural products in genetically engineered Escherichia coli and Saccharomyces cerevisiae.
在人类历史进程中，天然产物一直是用于治疗从心血管疾病到癌症等各类疾病的治疗药物发现和开发的基础。它们的化学多样性和复杂性为小分子药物提供了结构框架，并且一直是药物设计的灵感来源。然而，天然产物的化学复杂性也是这些药物进行工业规模生产的主要障碍之一。天然产物的化学合成通常困难且昂贵，从天然来源进行分离的产率通常也很低。合成生物学和代谢工程提供了一种替代方法，随着工程微生物工具的进一步发展，这种方法正变得越来越可行。通过在遗传上易于操作的宿主生物体中重建异源代谢途径，可以通过大规模发酵过程从廉价的糖类起始原料生产复杂的天然产物。在这篇观点文章中，我们讨论了旨在利用基因工程大肠杆菌和酿酒酵母生产萜类天然产物的正在进行的研究。
