Alkaloid chemodiversity in Mandragora spp. is associated with loss-of-functionality of MoH6H, a hyoscyamine 6β-hydroxylase gene

Further Insights on the <i>Datura innoxia</i> Hyoscyamine 6<i>β</i>-Hydroxylase (DiH6H) Based on Biochemical Characterization and Molecular Modeling

“…Hashimoto and Yamada (1986) [10] showed that the hyoscyamine 6β-hydroxylase from Hyoscyamus niger preferentially accepted the L-(2'S) isomer of hyoscyamine as a substrate and that the D-(2'R) isomer of hyoscyamine was nearly inactive. This was further corroborated in the recombinant MaH6H from Mandragora autumnalis [11] that encodes an active H6H enzyme. Still, a possible mechanism for this enantiomeric preference was not explained.…”

“…Still, a possible mechanism for this enantiomeric preference was not explained. Moreover, Schlesinger et al (2019) [11] showed that a substitution of the Gly-220 residue for a cysteine was linked to the lack of scopolamine and anisodamine phenotypes in M. officinarum accessions. Although M. officinarum accessions displayed a functionally inactive H6H, and this amino acid substitution was strongly linked with the alkaloid composition phenotype as determined by cleaved amplified polymorphic sequences (CAPS) analysis, the direct influence on the functionality of the specific Gly-220 substitution as related to other amino acid changes in the H6H protein was not tested.…”

“…Red X designate inefficient biochemical processes. The carbon numbering system for each compound is according to [11].…”

“…The procedure was essentially as described in [11]. In brief, the plasmids containing each gene were introduced to the expression strain E. coli BL21 (DE3).…”

Tropane alkaloid contamination of agricultural commodities and food products in relation to consumer health: Learnings from the 2019 Uganda food aid outbreak

“…As such, evidence of their use for medicinal applications in numerous cultures throughout history has been well documented (Mairura & Setshogo, 2014; Suk & Kwak, 2009). Both hyoscyamine and scopolamine are used in modern medicine as an antidote for organophosphate poisoning and for treatment of pain and nausea symptoms (Schlesinger et al., 2019). Furthermore, various plant parts are used as local remedies in treating several health disorders in many African countries (Bellakhdar, 1997; Mairura & Setshogo, 2014; Mwine, 2009; Mwine, Van Damme, Kudamba, Nasuuna, & Jumba, 2011; Nuwagaba, 2016).…”