Abstract
Terpenoids are a group of natural products that have a variety of essential and non-essential roles in metabolism, in biotic and abiotic interactions, as well as commercial applications such as pharmaceuticals, food additives, and chemical feedstocks. Economic viability for commercial applications is commonly not achievable by using natural source organisms or chemical synthesis. Engineered bio-production in suitable heterologous hosts is often required to achieve commercial viability. However, our poor understanding of regulatory mechanisms and other biochemical processes makes obtaining efficient conversion yields from feedstocks challenging. Moreover, production from carbon dioxide via photosynthesis would significantly increase the environmental and potentially the economic credentials of these processes by disintermediating biomass feedstocks. In this paper, we briefly review terpenoid metabolism, outline some recent advances in terpenoid metabolic engineering, and discuss why photosynthetic unicellular organisms—such as algae and cyanobacteria—might be preferred production platforms for the expression of some of the more challenging terpenoid pathways.
Highlights
Terpenoids are a chemically diverse class of natural products that are present in all domains of life and number in the tens of thousands of compounds isolated to date
The wealth of terpenoid structures provides a variety of roles in central cellular processes
Terpenoid biosynthesis starts with two non-homologous metabolic routes including the mevalonate (MVA) and the methyl-D-erythritol (MEP) pathways
Summary
Terpenoids are a chemically diverse class of natural products that are present in all domains of life and number in the tens of thousands of compounds isolated to date (more than 70,000 according to the Dictionary of Natural Products database). Terpenoid biosynthesis starts with two non-homologous metabolic routes including the mevalonate (MVA) and the methyl-D-erythritol (MEP) pathways. These pathways produce the universal 5-carbon prenyl phosphate precursor molecules isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) (Figure 1). Additions of IPP produce higher-order prenyl phosphates (module II), dephosphorylation (often coincident with or followed by bond rearrangement and/or cyclisation) to form specialized terpenoid backbones (module III), chemical decorations, and other modifications to yield end products. The industrial workhorses Escherichia coli and Saccharomyces cerevisiae (yeast) have been the primary target hosts They are well-characterized heterologous systems with a defined terpenoid background, which facilitates the analytics process and allows the expression of enzymes one by one, or in combinations. We explore advances in engineering photosynthetic microorganisms and discuss their potential as alternative production platforms for heterologous terpenoids
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