Identifying and engineering the ideal microbial terpenoid production host

Abstract

More than 70,000 different terpenoid structures are known so far; many of them offer highly interesting applications as pharmaceuticals, flavors and fragrances, or biofuels. Extraction of these compounds from their natural sources or chemical synthesis is-in many cases-technically challenging with low or moderate yields while wasting valuable resources. Microbial production of terpenoids offers a sustainable and environment-friendly alternative starting from simple carbon sources and, frequently, safeguards high product specificity. Here, we provide an overview on employing recombinant bacteria and yeasts for heterologous de novo production of terpenoids. Currently, Escherichia coli and Saccharomyces cerevisiae are the two best-established production hosts for terpenoids. An increasing number of studies have been successful in engineering alternative microorganisms for terpenoid biosynthesis, which we intend to highlight in this review. Moreover, we discuss the specific engineering challenges as well as recent advances for microbial production of different classes of terpenoids. Rationalizing the current stages of development for different terpenoid production hosts as well as future prospects shall provide a valuable decision basis for the selection and engineering of the cell factory(ies) for industrial production of terpenoid target molecules.

Improved cis-Abienol production through increasing precursor supply in Escherichia coli

“…As a typical diterpene, the expanding applications and growing demands of cis-abienol, which was raw material for Ambrox synthesis and a spice additive in cigarettes, have led to a widespread search for effective and economical manufacturing methods. Microorganisms provide a sustainable and environment-friendly alternative for the production of terpenoids, starting from simple carbon sources and, frequently, ensuring high product specificity 13 . Many biotechnological studies have focused on using E. coli as host for efficiently producing desired isoprenoids, in particular, the introduction of heterologous MVA pathway genes into E. coli has been very effective in improving productivity.…”

Yarrowia lipolytica Strains Engineered for the Production of Terpenoids

“…Production of terpenoids by fermentation using engineered cell factories can be cheaper and more sustainable than chemical synthesis. Indeed, hosts like the yeast Saccharomyces cerevisiae have been engineered to produce a variety of terpenoids and some of these cell factories are currently used industrially (Moser and Pichler, 2019). For example, the sesquiterpene β-farnesene is being produced industrially by highly engineered S. cerevisiae with titers of 130 g/L reported in the literature (Meadows et al, 2016).…”

Ustilago maydisserves as a novel production host for the synthesis of plant and fungal sesquiterpenoids

“…Sesquiterpenoids, for example, contain three and diterpenoids consist of four of such building blocks, forming C15 and C20 scaffolds, respectively. Terpenoids exhibit a plethora of biological functions like photoprotection, hormone signalling and defence against pathogens (Schmidt-Dannert, 2015;Troost et al, 2019;Moser and Pichler, 2019). Because of these diverse bioactivities they are also of interest for biotechnology.…”

“…Artemisin, for example, functions as antimalarial drug and (-)-patchoulol serves as a valuable fragrance for the cosmetics industry. Lycopene and (+)valencene are natural food additives (Schempp et al, 2018;Moser and Pichler, 2019).…”