Enzymatic cyclization of 26- and 27-methylidenesqualene to novel unnatural C31 polyprenoids by squalene:hopene cyclase

Squalene:hopene cyclase (SHC) from Alicyclobacillus acidocaldarius accepted 26-methylidenesqualene (26-MS) and 27-methylidenesqualene (27-MS) as a substrate and converted to novel pentacyclic C31 polyprenoids; a dammarene derivative with a 6.6.6.5+6 ring system and 26-methylidene-hop-22(29)-ene, respectively. The broad substrate specificity of the enzyme provided important information on the structure and function of SHC. Interestingly, 27-MS was also found to be a potent inhibitor of the bacterial SHC (IC50=5 μM), while 26-MS just showed poor enzyme inhibition (IC50=ca. 100 μM).