Carsanba Erdem, Pintado Manuela, Oliveira Carla
Amyris BioProducts Portugal, Unipessoal, Lda. Rua Diogo Botelho 1327, 4169-005 Porto, Portugal.
CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Universidade Católica Portuguesa, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal.
Pharmaceuticals (Basel). 2021 Mar 26;14(4):295. doi: 10.3390/ph14040295.
Terpenoids, also known as isoprenoids, are a broad and diverse class of plant natural products with significant industrial and pharmaceutical importance. Many of these natural products have antitumor, anti-inflammatory, antibacterial, antiviral, and antimalarial effects, support transdermal absorption, prevent and treat cardiovascular diseases, and have hypoglycemic activities. Production of these compounds are generally carried out through extraction from their natural sources or chemical synthesis. However, these processes are generally unsustainable, produce low yield, and result in wasting of substantial resources, most of them limited. Microbial production of terpenoids provides a sustainable and environment-friendly alternative. In recent years, the yeast has become a suitable cell factory for industrial terpenoid biosynthesis due to developments in omics studies (genomics, transcriptomics, metabolomics, proteomics), and mathematical modeling. Besides that, fermentation development has a significant importance on achieving high titer, yield, and productivity (TYP) of these compounds. Up to now, there have been many studies and reviews reporting metabolic strategies for terpene biosynthesis. However, fermentation strategies have not been yet comprehensively discussed in the literature. This review summarizes recent studies of recombinant production of pharmaceutically important terpenoids by engineered yeast, , with special focus on fermentation strategies to increase TYP in order to meet industrial demands to feed the pharmaceutical market. Factors affecting recombinant terpenoids production are reviewed (strain design and fermentation parameters) and types of fermentation process (batch, fed-batch, and continuous) are discussed.
萜类化合物，也被称为类异戊二烯，是一类广泛且多样的植物天然产物，在工业和制药领域具有重要意义。这些天然产物中的许多都具有抗肿瘤、抗炎、抗菌、抗病毒和抗疟疾作用，支持透皮吸收，预防和治疗心血管疾病，以及具有降血糖活性。这些化合物的生产通常通过从天然来源提取或化学合成来进行。然而，这些过程通常不可持续，产量低，并且导致大量资源的浪费，其中大多数资源有限。萜类化合物的微生物生产提供了一种可持续且环保的替代方法。近年来，由于组学研究（基因组学、转录组学、代谢组学、蛋白质组学）和数学建模的发展，酵母已成为工业萜类生物合成的合适细胞工厂。除此之外，发酵工艺的发展对于实现这些化合物的高滴度、高产量和高生产率（TYP）具有重要意义。到目前为止，已经有许多研究和综述报道了萜类生物合成的代谢策略。然而，发酵策略尚未在文献中得到全面讨论。本综述总结了利用工程酵母重组生产具有重要药用价值的萜类化合物的最新研究，特别关注提高TYP以满足制药市场工业需求的发酵策略。综述了影响重组萜类化合物生产的因素（菌株设计和发酵参数），并讨论了发酵过程的类型（分批发酵、补料分批发酵和连续发酵）。
