Metabolic engineering strategies to overcome precursor limitations in isoprenoid biosynthesis

Abstract

Isoprenoid biosynthesis has been a focus of metabolic engineering due to the broad spectrum of uses of isoprenoid products and the limited capacity to source them from plants or chemically synthesize them. Microbial synthesis offers the potential to cost-effectively produce isoprenoids in a stable and scalable manner. One bottleneck in advancing microbial engineering for isoprenoid biosynthesis has been limited supply of precursor molecules to the isoprenoid pathway. This article reviews strategies that have been employed to overcome such limitations. These include methods for enhancing reactions in the native pathway and preventing substrate depletion by competing pathways, the use of heterologous enzymes and pathways, and methods that reduce the metabolic burden imposed by heterologous reactions. Additionally, this article discusses challenges for the synthesis of novel products and maps some new directions for future research.