Mycobacterium tuberculosis, (Zopf, 1883) Lehmann & Neumann, 1896

Pu, Xue-Juan, Hu, Qian-Yi, Li, Su-Su, Li, Guo-Hong & Zhao, Pei-Ji, 2021, Sesquiterpenoids and their quaternary ammonium hybrids from the mycelium of mushroom Stereum hirsutum by medium optimization, Phytochemistry (112852) 189, pp. 1-8 : 5

2.3. Anti-M. tuberculosis activity

Stereumamides I–K (3–5), and sterostrein Q (11) were assayed for antibacterial activity against M. tuberculosis . All of the tested compounds exhibited weak antibacterial activities. MIC 50 values of stereumamides I–K (3–5) and sterostrein Q (11) against M. tuberculosis were 250, 250, 250, and 125 μg/mL, respectively.

Analysis of the genomic data revealed that the fungal genome contains a large number of clusters of specialised metabolite biosynthesis genes. In our previous review, the metabolite biosynthesis gene clusters of 18 fungi with published genomes were analyzed and predicted using antiSMASH 5.0 ( Blin et al., 2019; Lei and Zhao, 2019). The genome size of these fungi was generally 28–52 Mbp, and the predicted number of possible metabolite biosynthetic gene clusters ranged from 23 to 85, with most fungi having around 40 specialised metabolite biosynthetic gene clusters ( Lei and Zhao, 2019). Nielsen analyzed nine strains of fungi of the genus Penicillium , and the analysis showed that these nine strains had a large number of polyketones and nonribosomal peptide compound types of biosynthetic gene clusters, but only 16% of the clusters produced the corresponding metabolites ( Nielsen et al., 2017). Those data suggest that most fungi may have the potential to produce abundant metabolites.

In microbial fermentation research, researchers know that the culture conditions of a microorganism are critical to the diversity and abundance of metabolites. Zeeck and colleagues formalized an approach named OSMAC, which means that a microbial strain is able to produce different natural products when cultivated under various conditions. In recent years, a series of structurally undescribed compounds with multiple activities have been isolated and identified from fungi by the OSMAC strategy. The fermented mycelia of S. hirsutum have been reported to produce abundantly active metabolites ( Tian et al., 2020). After Dimitrios Floudas reported the whole genome of S. hirsutum FP-91666, we found that several terpene synthase gene clusters, six polyketide synthase gene clusters, and one polyketide synthase nonribosomal polypeptide heterodimer gene cluster are present in S. hirsutum ( Lackner et al., 2012) .

Stereum hirsutum can often serve as a host to algae and is even parasitized by the fungus Tremella aurantia to form the heterogeneous complex basidiocarp Jin’ er (golden jelly fungus) ( Bandoni and Zang, 1990; Liu and S.F, 1994), which has been traditionally used as food and crude medicine in Chinese society ( Dai and Yang, 2008). According to “Chinese Medicinal Fungi”, basidiocarp Jin’ er can be used to treat lung heat, cough, asthma, and hypertension. In our previous work, we isolated and identified some quaternary ammonium compounds of sesquiterpenes and amino acids from YMG medium, but the content was low. At present, we have further discovered some quaternary ammonium compounds through the OSMAC strategy ( Duan et al., 2018; Hu et al., 2020) and isolated a drimane-type sesquiterpene from the strain for the first time. These sesquiterpenoids and their quaternary ammonium compounds showed weak antibacterial activities, which is found in the mycelium of S. hirsutum and would suggest heterogeneous complex basidiocarp to be a functional food and veritable folk medicine.