# Biotechnological Fungal Platforms for the Production of Biosynthetic Cannabinoids
## 2 Chemical Structure of Cannabinoids, Types, and Metabolic Routes for Biosynthesis
\(\Delta^{9}\)-THCA, CBDA, and CBDA with a pentyl side chain are the end-products of the enzymatic biosynthesis of cannabinoids and are synthesized in the apoplastic space. These  
obesity, convulsive disorder, and rheumatoid arthritis. Furthermore, CBD also exhibits anti-psychotic, anti-nausea, and anti-anxiety properties [37]. In addition to the legal cannabis market (including medical and recreational uses), the EMCDDA (European Monitoring Centre for Drugs and Drug Addiction) estimated the illicit cannabis market in 2017 to be around 1.4-1.7 tones, valued at EUR 10.5-12.8 billion [38]. Several clinical uses of cannabinoids have been described, but just a few are legally recognized by international regulatory agencies. The possible clinical applications of CBD have been summarized in sixteen diseases, which included several cancer types through anti-proliferative and anti-invasive action; inflammatory bowel and Chron's diseases; cardiovascular diseases through anti-oxidant and anti-inflammatory properties; and neurodegenerative diseases (e.g., Parkinson's and Alzheimer's) [13]. However, in January 2020 the US Food and Drug Administration (FDA), FDA and Cannabis: Research and Drug Approval Process: [[https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process](https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process)]([https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process](https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process)) (accessed on 1 February 2023) indicated that up to that date just one cannabis-derived drug product had been approved, Epidiolex, containing a purified form of CBD involved in the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older. In addition, three synthetic cannabis-related drug products have been validated by the FDA: (i) Marinol (dronabinol); (ii) Syndros (dronabinol); and (iii) Cesamet (nabilone). On the one hand, Marinol and Syndros represent a synthetic version of THC, the psychoactive component of cannabis, for the treatment of nausea due to cancer chemotherapy and anorexia, thus preventing weight loss in AIDS patients. On the other hand, Cesamet has a chemical synthetic structure similar to THC as an active ingredient, which is used to treat nausea associated with cancer chemotherapy. Thus, in summary, cannabis as a hemp fiber is an economical reality, but the most promising market comprises the medical and recreative uses of the plant. However, the botanical derivatives are scarce in the legal market due to the putative risk of co-purification with other cannabinoids during the extraction process from naturally occurring plants. Nowadays, synthetic products are on the market through companies such as AbbVie Inc.; Corpus Pharmaceuticals Holdings Inc.; INSYS Therapeutics Inc.; and Bausch Health, although chemical synthesis is a costly process involving the use of chemicals that are not environmentally friendly. Nevertheless, synthetic production has paved the way for the biotechnological production of single cannabinoid compounds or derivatives in microorganisms, mainly fungi, which have been endowed with the biochemical machinery to reproduce the plant pathways and products [39], an approach that has been promoted by the development of recent synthetic biology methodologies [40].