Terpenoid Metabolic Engineering in Photosynthetic Microorganisms

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.

Functional Genomics Differentiate Inherent and Environmentally Influenced Traits in Dinoflagellate and Diatom Communities

“…Carotenoids, for example, are known to be produced in large quantities in diatoms [83] and serve several functions at higher trophic levels, e.g., as antioxidants due to their effects on the immune system and involvement in vision or body coloration [84]. Diatoms are further known to contribute a major proportion of marine volatile isoprene, which can have regional effects on oceanic climate [85,86]. The positive association of diatoms with the metabolic pathway genes of these compounds in our study is not surprising but has not yet been described before using metatranscriptomics data from field samples.…”

Emerging Technologies in Algal Biotechnology: Toward the Establishment of a Sustainable, Algae-Based Bioeconomy

“…As plant secondary metabolites, these compounds are typically produced in trace amounts; therefore industrial extraction ex planta requires very large quantities of biomass, with high economic and environmental costs. This could be averted with microalgae engineered to produce these chemicals in higher concentrations than is possible in plants (Arendt et al, 2016;Moses et al, 2017;Vavitsas et al, 2018;Lauersen, 2019). Cyanobacteria, for example, have been widely used for heterologous plant-derived terpenoid engineering, extensively reviewed in Chaves and Melis (2018) and Lin and Pakrasi (2019), and proof-of-concept works have unveiled the potential of engineered eukaryotic microalgae such as C. reinhardtii in producing high value terpenoids such as the food flavoring and aromas sesquiterpenoid patchulol and (E)α-bisabolene (Lauersen et al, 2016;Wichmann et al, 2018) and diterpenoids such as casbene, taxadiene, and 13R(+)manoylnyl oxide , as well as lambdane diterpenoids (Papaefthimiou et al, 2019), which are relevant precursors of plant-derived therapeutic and cosmetic products.…”

“…Many algal species are naturally efficient producers of carbohydrates, lipids, proteins, pigments, as well as a range of commercial secondary metabolites that are currently sourced from conventional agriculture (Koyande et al, 2019). Also, microalgae are emerging as a next-generation, cell-sized biofactories for the sustainable manufacturing of a myriad of products (Rasala and Mayfield, 2015;Vavitsas et al, 2018), following the example of established microbial platforms such as yeasts and bacteria. In this respect, microalgal biofactories have the potential to be less expensive and more sustainable platforms that may be naturally predisposed to produce certain plant-derived products (Vavitsas et al, 2018).…”

High density cultivation for efficient sesquiterpenoid biosynthesis inSynechocystissp. PCC 6803

“…Thereby, the initial cell densities were adjusted to OD750 ~0. 25. Each strain was cultivated in quadruplicate from the same pre-culture.…”

“…Classical screening setups for terpenoid production in cyanobacteria involve photoautotrophic batch cultivation in shaking flasks or aerated vessels supplied with bubble columns of CO2-enriched air. When calculated to standardized time frames of four days, these protocols result in rather dilute cultivation setups as well as low volumetric product titers of up to ~8 mg * L -1 or specific titers of up to ~20 mg * g -1 DCW, respectively [summarized in 3,25]. An appreciable exception is a study on production of the volatile compound isoprene in Synechococcus elongatus PCC 7942, for which volumetric titers of more than 400 mg * L -1 were reported in 4 days [13].…”