Diversifying Isoprenoid Platforms via Atypical Carbon Substrates and Non-model Microorganisms.

David N Carruthers,Taek Soon Lee

doi:10.3389/fmicb.2021.791089

David N Carruthers, Taek Soon Lee

Open Access

https://doi.org/10.3389/fmicb.2021.791089

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Abstract

Isoprenoid compounds are biologically ubiquitous, and their characteristic modularity has afforded products ranging from pharmaceuticals to biofuels. Isoprenoid production has been largely successful in Escherichia coli and Saccharomyces cerevisiae with metabolic engineering of the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways coupled with the expression of heterologous terpene synthases. Yet conventional microbial chassis pose several major obstacles to successful commercialization including the affordability of sugar substrates at scale, precursor flux limitations, and intermediate feedback-inhibition. Now, recent studies have challenged typical isoprenoid paradigms by expanding the boundaries of terpene biosynthesis and using non-model organisms including those capable of metabolizing atypical C1 substrates. Conversely, investigations of non-model organisms have historically informed optimization in conventional microbes by tuning heterologous gene expression. Here, we review advances in isoprenoid biosynthesis with specific focus on the synergy between model and non-model organisms that may elevate the commercial viability of isoprenoid platforms by addressing the dichotomy between high titer production and inexpensive substrates.

Highlights

Isoprenoids are ubiquitous across all domains of life and span a wide and varied range of natural products
We focused on improvements to isoprenoid precursor biosynthesis and translation of enzymes or pathways between organisms, which could assist in overcoming current major barriers to commercial viability (Zu et al, 2020)
We have described works that capitalized upon the modularity of isoprenoid advances through heterologous expression of entire pathways

Summary

Introduction

Isoprenoids are ubiquitous across all domains of life and span a wide and varied range of natural products. E. coli endogenously generates isoprenoids through the MEP pathway while S. cerevisiae utilizes its native MVA pathway, together enabling researchers to combine synthetic biological toolkits with the abundance of information of these strains to facilitate high-titer isoprenoid production. Neither E. coli or S. cerevisiae naturally accumulate isoprenoids at high titer and bioproduction is often limited to heavily modified strains with inducible episomal expression systems.

Results

Conclusion