Enzymatic synthesis of unnatural cyclic triterpenes

Abstract

The broad substrate tolerance and catalytic potential of bacterial squalene cyclases and plant oxidosqualene cyclases are remarkable; the enzymes accept a wide variety of nonphysiological substrate analogues and efficiently perform sequential ring-forming reactions to produce a series of unnatural cyclic triterpenes. By utilizing such properties of the enzymes, it is possible to generate unnatural novel cyclic polyprenoids by enzymatic conversion of chemically synthesized substrate analogues. Here we present recent examples including (a) enzymatic formation of a “supranatural” hexacyclic polyprenoid as well as heteroaromatic ring containing cyclic polyprenoids by bacterial squalene–hopene cyclase from Alicyclobacillus acidocaldarius and (b) enzymatic cyclization of 22,23-dihydro-2,3-oxidosqualene and 24,30-bisnor-2,3-oxidosqualene by plant oxidosqualene-β-amyrin cyclase from Pisum sativum.