“∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD) are the most abundant natural cannabinoids isolated from the different cultivars of the Cannabis plant. Other natural ∆9-THC analogs, especially those with different alkyl chain substitutions, display different and potent bioactivity. However, these rare cannabinoids are typically isolated at minuscule amounts and are difficult to synthesize. Targeted microbial biosynthesis can therefore be an attractive route to access such molecules.

Here, we report the development of a Saccharomyces cerevisiae host to biosynthesize two rare cannabinoids from simple sugars. The yeast host is engineered to accumulate excess geranyl pyrophosphate (GPP), to overexpress a fungal pathway to 2,4-dihydroxy-6-alkyl-benzoic acids, as well as the downstream UbiA-prenyltransferase and THCA synthase. Two rare cannabinoid acids, the C1-substituted ∆9-tetrahydrocannabiorcolic acid (∆9-THCCA, ∼16 mg/L) and the C7-substituted ∆9-tetrahydrocannabiphorolic acid (∆9-THCPA, ∼5 mg/L) were obtained from this host; the latter was thermally decarboxylated to give ∆9-tetrahydrocannabiphorol (∆9-THCP).

Given the diversity of fungal biosynthetic gene clusters (BGCs) that can produce resorcylic acids, this microbial platform offers potential to produce other rare and new-to-nature cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/40359163/

https://academic.oup.com/jimb/advance-article/doi/10.1093/jimb/kuaf013/8129704?login=false

“The total flavonoids of Cannabis sativa L. were selected as the research object, and the extraction process of C. sativa L. was optimized on the basis of a single factor experiment utilizing a five-factor, three-level response surface method. Subsequently, the vitro antimicrobial and antioxidant activities of the flavonoids were evaluated.

The optimized extraction conditions were as follows: ratio of liquid to solid, 24.69:1 mL/g; soaking time, 102.12 min; extraction time, 165.96 min; ethanol concentration, 46.59%; extraction temperature, 86.87 °C. The extraction rate of C. sativa L. flavonoids (CSF) was found to be 5.51 ± 0.04 mg/g. The extraction of crude flavonoid (i.e., flavonoids extracted under the optimal extraction process) was conducted using four solvents, resulting in five C. sativa L. flavonoid extracts (petroleum ether, CSF_p; n-butanol, CSF_b; ethyl acetate, CSF_e; aqueous phase, CSF_w; and crude flavonoid, CSF). CSF contains 10 flavonoid components.

In vitro, all five CSF samples demonstrated good total reducing power, effective scavenging capacity against DPPH and ABTS⁺ radicals, and pronounced inhibitory effects against Escherichia coli, Bacillus subtilis, and Bacillus pumilus. Analytic Hierarchy Process (AHP) was employed to evaluate the five CSF samples in terms of antibacterial and antioxidant activity.

The results indicated that petroleum-ether-extracted C. sativa L. flavonoids (CSF_p) exhibited the most pronounced antibacterial and antioxidant effects.”

https://pubmed.ncbi.nlm.nih.gov/40352509/

“Cannabis sativa L. is an annual herbaceous plant belonging to the mulberry family. It has been demonstrated that the plant contains a variety of physiologically active substances, including antibacterial, antithrombotic, antiallergic, and analgesic properties.”

“The results demonstrate that flavonoids present in C. sativa L. possess significant potential for utilization in both medical and industrial applications.”

https://pubs.acs.org/doi/10.1021/acsomega.4c10986

“This study aimed to investigate the antibacterial effects and mechanism of cannabigerol against drug-resistant Streptococcus iniae.

The determination of antibacterial activity was based on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), growth curve analysis, time-kill assay, biofilm inhibition and eradication assessments.

The antibacterial mechanism was explored by DNA leakage assay, assessment of cell membrane permeability, evaluation of cell membrane integrity, measurement of membrane potential, determination of respiratory chain dehydrogenase activity, and examination by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

The results demonstrated that cannabigerol effectively inhibited the growth and biofilm formation of Streptococcus iniae in vitro.

Mechanistically, cannabigerol induced DNA leakage, impaired cell membrane integrity, hyperpolarized membrane potential, and reduced respiratory chain dehydrogenase activity in S. iniae.

In conclusion, these findings suggest that cannabigerol inhibited the growth of S. iniae by disrupting the cell membrane.”

https://pubmed.ncbi.nlm.nih.gov/40146372/

“In the scenario of fighting bacterial resistance to antibiotics, natural products have been extensively investigated for their potential antibacterial activities. Among these, cannabinoids-bioactive compounds derived from cannabis-have garnered attention for their diverse biological activities, including anxiolytic, anti-inflammatory, analgesic, antioxidant, and neuroprotective properties.

Emerging evidence suggests that cannabinoids may also possess significant antimicrobial properties, with potential applications in enhancing the efficacy of conventional antimicrobial agents. Therefore, this review examines evidence from the past five years on the antimicrobial properties of cannabinoids, focusing on underlying mechanisms such as microbial membrane disruption, immune response modulation, and interference with microbial virulence factors. In addition, their synergistic potential, when used alongside standard therapies, underscores their promise as a novel strategy to address drug resistance, although further research and clinical trials are needed to validate their therapeutic use.

Overall, cannabinoids offer a promising avenue for the development of innovative treatments to combat drug-resistant infections and reduce the reliance on traditional antimicrobial agents.”

https://pubmed.ncbi.nlm.nih.gov/40005695/

“The unique chemical properties of cannabinoids, combined with their interactions with existing therapies, contribute to their antimicrobial effects against a wide range of microorganisms, including bacteria, fungi, and viruses.The data collected support the conclusion that cannabinoids exert their effects through multiple pathways, including the disruption of microbial membranes, modulation of immune responses, and interference with microbial virulence factors.

The use of cannabinoids as alternative therapeutic options has demonstrated their potential to overcome the limitations of conventional antibiotics, offering a potential new approach to combating drug-resistant microorganisms, potentially reducing dependence on traditional antimicrobial agents that have become less effective. It also appears that the use of combinations of cannabinoids with other conventional drugs can potentially lead to a synergistic effect with improved therapeutic capabilities.”

https://www.mdpi.com/2076-2607/13/2/325

“Cannabidiol (CBD), the primary non-psychoactive cannabinoid isolated from cannabis, exhibits promising antibacterial effects. However, the antibacterial mechanism of CBD remains poorly understood.

In this study, the mechanism was investigated using bacterial inhibition assays, label-free proteomics, and untargeted metabolomics, with Bacillus licheniformis (B. licheniformis), Staphylococcus aureus (S. aureus), and Enterococcus faecium (E. faecium) selected as representative Gram-positive bacteria.

The results revealed that CBD caused significant damage to bacterial cell walls and membranes, leading to notable changes in proteomic and metabolic profiles. Specifically, 437, 120, and 195 proteins, as well as 52, 153, and 94 metabolites, were differentially expressed in B. licheniformis, S. aureus, and E. faecium, respectively.

The antimicrobial mechanism of CBD shares similarities with previously known antibacterial agents, such as penicillin and cephalosporins, particularly in affecting the bacterial cell wall, but differs in its detailed mode of action. CBD disrupted the biosynthesis of primary and secondary metabolites and altered bacterial metabolism, contributing to its antibacterial activity.

This study provides valuable insights into the antibacterial mechanism of CBD, supporting its potential development as an antibiotic alternative and its application in food safety.

SIGNIFICANCE: It is crucial to find alternatives to antibiotics to mitigate the impact of pathogenic bacteria on food safety and reduce the use of antibiotics. CBD is the primary non-psychoactive cannabinoid derived from cannabis, and it has shown promising antibacterial effects. However, the antimicrobial mechanisms of CBD have not been well elucidated. This study provides a deep understanding of the antibacterial mechanism from the cellular to molecular level, which will contribute to the development of CBD as a novel antibacterial agent.”

https://pubmed.ncbi.nlm.nih.gov/39978755/

“CBD is a promising antibacterial agent for Gram-positive bacteria.”

https://www.sciencedirect.com/science/article/abs/pii/S1874391925000387?via%3Dihub