CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, Uttar Pradesh, India; School of Agricultural Biotechnology, Punjab Agricultural University, Ludhiana 141004, Punjab, India.
CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, Uttar Pradesh, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, Uttar Pradesh, India.
Biotechnol Adv. 2023 Nov;68:108214. doi: 10.1016/j.biotechadv.2023.108214. Epub 2023 Jul 20.
Triterpenoids are among the most assorted class of specialized metabolites found in all the taxa of living organisms. Triterpenoids are the leading active ingredients sourced from plant species and are utilized in pharmaceutical and cosmetic industries. The triterpenoid precursor 2,3-oxidosqualene, which is biosynthesized via the mevalonate (MVA) pathway is structurally diversified by the oxidosqualene cyclases (OSCs) and other scaffold-decorating enzymes such as cytochrome P450 monooxygenases (P450s), UDP-glycosyltransferases (UGTs) and acyltransferases (ATs). A majority of the bioactive triterpenoids are harvested from the native hosts using the traditional methods of extraction and occasionally semi-synthesized. These methods of supply are time-consuming and do not often align with sustainability goals. Recent advancements in metabolic engineering and synthetic biology have shown prospects for the green routes of triterpenoid pathway reconstruction in heterologous hosts such as Escherichia coli, Saccharomyces cerevisiae and Nicotiana benthamiana, which appear to be quite promising and might lead to the development of alternative source of triterpenoids. The present review describes the biotechnological strategies used to elucidate complex biosynthetic pathways and to understand their regulation and also discusses how the advances in triterpenoid pathway engineering might aid in the scale-up of triterpenoid production in engineered hosts.
三萜类化合物是所有生物分类群中最具多样性的一类特殊代谢产物。三萜类化合物是植物物种中提取的主要活性成分，被广泛应用于制药和化妆品行业。三萜类化合物的前体 2,3-氧化鲨烯通过甲羟戊酸 (MVA) 途径生物合成，其结构通过氧化鲨烯环化酶 (OSCs) 和其他支架修饰酶（如细胞色素 P450 单加氧酶 (P450s)、UDP-糖基转移酶 (UGTs) 和酰基转移酶 (ATs)）进行多样化。大多数生物活性三萜类化合物都是从天然宿主中采用传统的提取方法收获的，偶尔也会进行半合成。这些供应方法耗时且通常不符合可持续性目标。代谢工程和合成生物学的最新进展表明，在大肠杆菌、酿酒酵母和黄花烟等异源宿主中重建三萜类途径的绿色途径具有前景，这些方法似乎很有前途，可能会开发出三萜类化合物的替代来源。本综述描述了用于阐明复杂生物合成途径及其调控的生物技术策略，并讨论了三萜类途径工程的进展如何有助于在工程宿主中扩大三萜类化合物的生产规模。
