Kosalková Katarina, Barreiro Carlos, Sánchez-Orejas Isabel-Clara, Cueto Laura, García-Estrada Carlos
INBIOTEC (Instituto de Biotecnología de León), Av. Real 1, 24006 León, Spain.
Área de Bioquímica y Biología Molecular, Departamento de Biología Molecular, Campus de Vegazana, Universidad de León, 24007 León, Spain.
J Fungi (Basel). 2023 Feb 10;9(2):234. doi: 10.3390/jof9020234.
Cannabinoids are bioactive meroterpenoids comprising prenylated polyketide molecules that can modulate a wide range of physiological processes. Cannabinoids have been shown to possess various medical/therapeutic effects, such as anti-convulsive, anti-anxiety, anti-psychotic, antinausea, and anti-microbial properties. The increasing interest in their beneficial effects and application as clinically useful drugs has promoted the development of heterologous biosynthetic platforms for the industrial production of these compounds. This approach can help circumvent the drawbacks associated with extraction from naturally occurring plants or chemical synthesis. In this review, we provide an overview of the fungal platforms developed by genetic engineering for the biosynthetic production of cannabinoids. Different yeast species, such as (formerly ) and , have been genetically modified to include the cannabinoid biosynthetic pathway and to improve metabolic fluxes in order to increase cannabinoid titers. In addition, we engineered the filamentous fungus for the first time as a host microorganism for the production of Δ-tetrahydrocannabinolic acid from intermediates (cannabigerolic acid and olivetolic acid), thereby showing the potential of filamentous fungi as alternative platforms for cannabinoid biosynthesis upon optimization.
大麻素是一类生物活性半萜类化合物，由异戊烯基化的聚酮化合物分子组成，可调节多种生理过程。大麻素已被证明具有多种医学/治疗作用，如抗惊厥、抗焦虑、抗精神病、抗恶心和抗菌特性。人们对其有益作用以及作为临床有用药物的应用兴趣日益浓厚，这推动了用于这些化合物工业化生产的异源生物合成平台的发展。这种方法有助于规避与从天然植物中提取或化学合成相关的缺点。在本综述中，我们概述了通过基因工程开发的用于大麻素生物合成生产的真菌平台。不同的酵母物种，如（原）和，已通过基因改造纳入大麻素生物合成途径并改善代谢通量，以提高大麻素滴度。此外，我们首次将丝状真菌改造为宿主微生物，用于从中间体（大麻二酚酸和橄榄酸）生产Δ-四氢大麻酚酸，从而表明丝状真菌在优化后作为大麻素生物合成替代平台的潜力。
