Substitution of a histidine, comprising part of the catalytic base group in the ent-copalyl diphosphate synthases found in all seed plants for gibberellin phytohormone metabolism, by a larger aromatic residue leads to rearrangements. Through a series of 1,2-hydride and methyl shifts of the initially formed bicycle predominant formation of (−)-kolavenyl diphosphate is observed. Further mutational analysis and quantum chemical calculations provide mechanistic insight into the basis for this profound effect on product outcome.

Substitution of a histidine, comprising part of the catalytic base group in the ent-copalyl diphosphate synthases found in all seed plants for gibberellin phytohormone metabolism, by a larger aromatic residue leads to rearrangements. Through a series of 1,2-hydride and methyl shifts of the initially formed bicycle predominant formation of (−)-kolavenyl diphosphate is observed. Further mutational analysis and quantum chemical calculations provide mechanistic insight into the basis for this profound effect on product outcome.

An active-site water molecule coordinated by conserved histidine and asparagine residues seems to serve as the catalytic base in all ent-copalyl diphosphate synthases (CPSs). When these residues are substituted by alanine, the mutant CPSs produce stereochemically novel ent-8-hydroxy-CPP. Given the requisite presence of CPSs in all land plants for gibberellin phytohormone biosynthesis, such plasticity presumably underlies the observed extensive diversification of the resulting labdane-related diterpenoids.

An active-site water molecule coordinated by conserved histidine and asparagine residues seems to serve as the catalytic base in all ent-copalyl diphosphate synthases (CPSs). When these residues are substituted by alanine, the mutant CPSs produce stereochemically novel ent-8-hydroxy-CPP. Given the requisite presence of CPSs in all land plants for gibberellin phytohormone biosynthesis, such plasticity presumably underlies the observed extensive diversification of the resulting labdane-related diterpenoids.

Most types of ambers are naturally occurring, relatively hard, durable resinite polymers derived from the exudates of trees. This resource has been coveted for thousands of years due to its numerous useful properties in industrial processes, beauty, and purported medicinal properties. Labdane diterpenoid-based ambers represent the most abundant and important resinites on earth. These resinites are a dwindling nonrenewable natural resource, so a new source of such materials needs to be established. Recent advances in sequencing technologies and biochemical engineering are rapidly accelerating the rate of identifying and assigning function to genes involved in terpenoid biosynthesis, as well as producing industrial-scale quantities of desired small-molecules in bacteria and yeast. This has provided new tools for engineering metabolic pathways capable of producing diterpenoid monomers that will enable the production of custom-tailored resinite-like polymers. Furthermore, this biosynthetic toolbox is continuously expanding, providing new possibilities for renewing dwindling stocks of naturally occurring resinite materials and engineering new materials for future applications. © 2010 Wiley Periodicals, Inc. Biopolymers 95: 71–76, 2011.