Institute for Biological Sciences, University of Rostock, Albert-Einstein-Str. 3, 18059 Rostock, Germany.
Department of Plant Sciences, University of Tennessee, Knoxville, TN 37996, USA.
FEMS Microbiol Rev. 2021 Nov 23;45(6). doi: 10.1093/femsre/fuab024.
The 'biogenetic isoprene rule', formulated in the mid 20th century, predicted that terpenoids are biosynthesized via polymerization of C5 isoprene units. The polymerizing enzymes have been identified to be isoprenyl diphosphate synthases, products of which are catalyzed by terpene synthases (TPSs) to achieve vast structural diversity of terpene skeletons. Irregular terpenes (e.g, C11, C12, C16 and C17) are also frequently observed, and they have presumed to be synthesized by the modification of terpene skeletons. This review highlights the exciting discovery of an additional route to the biosynthesis of irregular terpenes which involves the action of a newly discovered enzyme family of isoprenyl diphosphate methyltransferases (IDMTs). These enzymes methylate, and sometimes cyclize, the classical isoprenyl diphosphate substrates to produce modified, non-canonical substrates for specifically evolved TPSs. So far, this new pathway has been found only in bacteria. Structure and sequence comparisons of the IDMTs strongly indicate a conservation of their active pockets and overall topologies. Some bacterial IDMTs and TPSs appear in small gene clusters, which may facilitate future mining of bacterial genomes for identification of irregular terpene-producing enzymes. The IDMT-TPS route for terpenoid biosynthesis presents another example of nature's ingenuity in creating chemical diversity, particularly terpenoids, for organismal fitness.
“生源异戊二烯规则”于 20 世纪中期提出，预测萜类化合物是通过 C5 异戊二烯单元的聚合生物合成的。现已鉴定出聚合酶为异戊烯二磷酸合酶，其产物由萜烯合酶（TPS）催化，从而实现萜烯骨架的巨大结构多样性。还经常观察到不规则萜类（例如，C11、C12、C16 和 C17），并且推测它们是通过萜烯骨架的修饰合成的。本文重点介绍了不规则萜类生物合成的另一种途径的令人兴奋的发现，该途径涉及新发现的异戊烯二磷酸甲基转移酶（IDMT）家族酶的作用。这些酶使经典的异戊烯二磷酸底物甲基化，有时环化，产生为特定进化的 TPS 产生的修饰的非典型底物。到目前为止，这种新途径仅在细菌中发现。IDMT 的结构和序列比较强烈表明其活性口袋和整体拓扑结构的保守性。一些细菌 IDMT 和 TPS 似乎存在于小基因簇中，这可能有助于未来挖掘细菌基因组以鉴定产生不规则萜类的酶。萜类生物合成的 IDMT-TPS 途径为生物体适应性创造化学多样性，特别是萜类化合物，提供了另一个例子。
