Department of Biochemistry, Michigan State University, East Lansing, MI, USA.
MelaTech, LLC, Baltimore, MD, USA.
Methods Mol Biol. 2024;2760:3-20. doi: 10.1007/978-1-0716-3658-9_1.
Terpenoids represent the most diverse class of natural products, with a broad spectrum of industrial relevance including applications in green solvents, flavors and fragrances, nutraceuticals, colorants, and therapeutics. They are typically challenging to extract from their natural sources, where they occur in small amounts and mixtures of related but unwanted byproducts. Formal chemical synthesis, where established, is reliant on petrochemistry. Hence, there is great interest in developing sustainable solutions to assemble biosynthetic pathways in engineered host organisms. Metabolic engineering for chemical production has largely focused on microbial hosts, yet plants offer a sustainable production platform. In addition to containing the precursor pathways that generate the terpenoid building blocks as well as the cell structures and compartments required, or tractable localization for the enzymes involved, plants may provide a low input system to produce these chemicals using carbon dioxide and sunlight only. There have been significant recent advancements in the discovery of pathways to terpenoids of interest as well as strategies to boost yields in host plants. While part of the phytochemical field is focusing on the discovery of biosynthetic pathways, this review will focus on advancements using the pathway toolbox and toward engineering plants for the production of terpenoids. We will highlight strategies currently used to produce target products, optimization of known pathways to improve yields, compartmentalization of pathways within cells, and genetic tools developed to facilitate complex engineering of biosynthetic pathways. These advancements in Synthetic Biology are bringing engineered plant systems closer to commercially relevant hosts for the bioproduction of terpenoids.
萜类化合物是天然产物中最多样化的一类，具有广泛的工业相关性，包括在绿色溶剂、香料和香精、营养保健品、着色剂和治疗剂中的应用。它们通常很难从天然来源中提取，因为它们的含量很少，而且与所需产物相关的不需要的副产品混合物也很多。如果有既定的方法，那么正式的化学合成是依赖于石油化学的。因此，人们非常有兴趣开发可持续的解决方案，以在工程宿主生物中组装生物合成途径。用于化学生产的代谢工程在很大程度上集中在微生物宿主上，但植物提供了一个可持续的生产平台。除了包含生成萜类化合物结构单元的前体途径以及所需的细胞结构和隔室，或者涉及的酶的可处理定位外，植物还可以提供一个低投入系统，仅使用二氧化碳和阳光来生产这些化学品。最近在发现萜类化合物的途径以及在宿主植物中提高产量的策略方面取得了重大进展。虽然植物化学领域的一部分专注于发现生物合成途径，但本综述将重点介绍使用途径工具箱和工程植物生产萜类化合物的进展。我们将重点介绍目前用于生产目标产品的策略、优化已知途径以提高产量、细胞内途径的区室化以及为促进生物合成途径的复杂工程而开发的遗传工具。这些合成生物学方面的进展使工程植物系统更接近于商业上相关的萜类化合物生物生产宿主。
