Kyle J. Lauersen

King Abdullah University of Science and Technology | KAUST · Department of Bioscience

Certain endangered Thymelaeaceous trees are major sources of the fragrant and highly valued resinous agarwood, comprised of hundreds of oxygenated sesquiterpenoids (STPs). Despite growing pressure on natural agarwood sources, the chemical complexity of STPs severely limits their synthetic production. Here, we catalogued the chemical diversity in 58...

The polyextremophilic Cyanidiophyceae are eukaryotic red microalgae with promising biotechnological properties arising from their low pH and elevated temperature requirements which can minimize culture contamination at scale. Cyanidioschyzon merolae 10D is a cell wall deficient species with a fully sequenced genome that is amenable to nuclear trans...

The west coast of the Arabian Peninsula borders the Red Sea, a water body which maintains high average temperatures and increased salinity compared to other seas or oceans. This geography has many resources which could be used to support algal biotechnology efforts in bio-resource circularity. However, summer conditions in this region may exceed th...

Isoprene is a clear, colorless, volatile 5-carbon hydrocarbon that is one monomer of all cellular isoprenoids and a platform chemical with multiple applications in industry. Many plants have evolved isoprene synthases (IspSs) with the capacity to liberate isoprene from dimethylallyl diphosphate (DMADP) as part of cellular thermotol- erance mechanis...

Wastewater (WW) treatment in anaerobic membrane bioreactors (AnMBR) is considered more sustainable than in aerobic reactors. However, outputs from AnMBR are a mixed methane and carbon dioxide gas stream as well as ammonium- (N) and phosphate- (P) containing waters. Using AnMBR outputs as inputs for photoautotrophic algal cultivation can strip the C...

Terpenoids play key roles in cellular metabolism and can have specialized functions. Their heterologous production in microbial hosts offers an alternative to natural extraction. Here, we developed a subcellular engineering approach in the model green alga Chlamydomonas reinhardtii by targeting both sesquiterpenoid synthases and cytochrome P450s (C...

The eukaryotic red alga Cyanidioschyzon merolae 10D is an emerging algal host for synthetic biology and metabolic engineering. Its small nuclear genome (16.5 Mb; 4775 genes), low intron content (39), stable transgene expression, and capacity for homologous recombination into its nuclear genome make it ideal for genetic and metabolic engineering end...

Chlamydomonas reinhardtii is a green microalga that has been genetically engineered to produce heterologous terpenoid metabolites. While this green biochemical approach for producing high-value chemicals holds tremendous potential, the current in situ extraction methods, utilizing traditional solvents such as dodecane and perfluorinated chemicals,...

Thymelaceaous trees are prized for accumulating fragrant resins composed of hundreds of secondary metabolites in their woody tissues. Slow growth and increasing consumer demand have stretched natural sources of agarwood trees to being endangered and alternative production modes, including silviculture and tissue culture, are currently being investi...

The high-value carotenoid astaxanthin is a powerful antioxidant with various purported health benefits. The alga Haematococcus lacustris (formerly pluvialis) represents the main natural (farmed) source of astaxanthin. Additionally, Chlamydomonas reinhardtii has been engineered to produce ketocarotenoids including canthaxanthin, astaxanthin, and int...

Terpenoids play key roles in cellular metabolism, with some organisms having evolved expanded terpenoid profiles for specialized functions such as signaling and defense. Many terpenoids have applications in pharmaceuticals, fragrances, and agriculture, but their harvest from natural sources can be challenging. Heterologous production of specialty t...

The eukaryotic red alga Cyanidioschyzon merolae 10D is an emerging algal host for synthetic biology and metabolic engineering. Its small nuclear genome (16.5 Mb; 4775 genes), low intron content (38), stable transgene expression, and capacity for homologous recombination into its nuclear genome make it ideal for genetic and metabolic engineering end...

In eukaryotic organisms, proteins are typically translated from monocistronic messenger RNAs containing a single coding sequence (CDS). However, recent long transcript sequencing identified 87 nuclear polycis-tronic mRNAs in Chlamydomonas reinhardtii natively carrying multiple co-expressed CDSs. In this study, we investigated the dynamics of 22 sho...

Algae are diverse organisms with significant biotechnological potential for resource circularity. Taking inspiration from fermentative microbes, engineering algal genomes holds promise to broadly expand their application ranges. Advances in genome sequencing with improvements in DNA synthesis and delivery techniques are enabling customized molecula...

Background: The colony-forming, green microalga Botryococcus braunii secretes large amounts of petroleum-like hydrocarbons, which enables non-destructive in situ extraction (milking) of these extracellular hydrocarbons during culture growth continuously without cell lysis. This study compares the suitability of 15 different solvents, including alka...

Certain endangered Thymelaeaceous trees are major sources of the fragrant and highly valued resinous agarwood, comprised of hundreds of oxygenated sesquiterpenoids (STPs). Despite growing pressure on natural agarwood sources, the chemical complexity of STPs severely limits synthetic production. Here, we catalogued the chemical diversity in 58 agarw...

Terpenoids, a family of natural compounds with various uses, are produced by many organisms, including plants, bacteria, and mammals. However, these specialty chemicals are currently being sourced in an unsustainable manner from slow-growing plants, such as the fragrant products of the Aquilaria tree, known in the Middle East as oud and bakhour. He...

Terpenoids are a diverse class of natural compounds with many applications, such as flavors and fragrances. Sesquiterpenoids (C15) are fragrant components of incenses and perfumes, which are widely used in the Middle East region. Some, however, are acquired unsustainably from slow-growing plants such as Aquilaria sp. trees, members of which are con...

Terpenoids are a diverse class of natural compounds with a wide range of applications in flavoring, fragrances, and medicine. However, many of these compounds are sourced from slow-growing, rare, or endangered plants. Heterologous production of terpenoids in engineered microbes offers a promising alternative which is scalable and readily accessible...

The polyextremophilic Cyanidiales are eukaryotic red microalgae with promising biotechnological properties arising from their low pH and elevated temperature requirements which can minimize culture contamination at scale. Cyanidioschyzon merolae 10D is a cell wall deficient species with a fully sequenced genome that is amenable to nuclear transgene...

Astaxanthin is a valuable ketocarotenoid with various pharmaceutical and nutraceutical applications. Green microalgae harbor natural capacities for pigment accumulation due to their 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway. Recently, a redesigned ß-carotene ketolase (BKT) was found to enable ketocarotenoid accumulation in the model microal...

The west coast of Saudi Arabia borders the Red Sea, which maintains high average temperatures and increased salinity compared to other seas or oceans. Summer conditions in the Arabian Peninsula may exceed the temperature tolerance of most currently cultivated microalgae. The Cyanidiales are polyextremophilic red algae whose native habitats are at t...

Greenhouse gas (GHG) emissions have created a global climate crisis which requires immediate interventions to mitigate the negative effects on all aspects of life on this planet. As current agriculture and land use contributes up to 25% of total GHG emissions, plant scientists take center stage in finding possible solutions for a transition to sust...

Isoprene is a clear, colorless, volatile 5-carbon hydrocarbon that is one monomer of all cellular isoprenoids and a platform chemical with multiple applications in industry. Many plants have evolved isoprene synthases (IspSs) with the capacity to liberate isoprene from dimethylallyl pyrophosphate (DMAPP) as part of cellular protection mechanisms. I...

Wastewater (WW) treatment in anaerobic membrane bioreactors (AnMBR) is considered more sustainable than in their aerobic counterparts. However, outputs from AnMBR are mixed methane and carbon dioxide gas streams as well as ammonium- (N) and phosphate- (P) containing waters. Using AnMBR outputs as inputs for photoautotrophic algal cultivation can st...

Fluorescent proteins (FPs) are powerful reporters with a broad range of applications in gene expression and subcellular localization. High-throughput screening is often required to identify individual transformed cell lines in organisms that favor non-homologous-end-joining integration of transgenes into genomes, like in the model green microalga C...

Background: Eukaryotic algae have recently emerged as hosts for metabolic engineering efforts to generate heter- ologous isoprenoids. Isoprenoid metabolic architectures, flux, subcellular localization, and transport dynamics have not yet been fully elucidated in algal hosts. Results: In this study, we investigated the accessibility of different iso...

Chlamydomonas reinhardtii is a model green microalga capable of heterotrophic growth on acetic acid but not fatty acids, despite containing a full complement of genes for β-oxidation. Recent reports indicate that the alga preferentially sequesters, rather than breaks down, lipid acyl chains as a means to rebuild its membranes rapidly. Here, we asse...

Background Autotrophic carbon fixation is the primary route through which organic carbon enters the biosphere, and it is a key step in the biogeochemical carbon cycle. The Calvin–Benson–Bassham pathway, which is predominantly found in plants, algae, and some bacteria (mainly cyanobacteria), was previously considered to be the sole carbon-fixation p...

Microbial production of heterologous metabolites is now a mature technology in many host organisms, opening new avenues for green production processes of specialty chemicals. At lab scale, petroleum- based hydrophobic bio-compatible solvents like dodecane can be used as a second phase on top of microbial cultures to act as a physical sink for heter...

The field of stress granules (SGs) has recently emerged in the study of the plant stress response, yet these structures, their dynamics and importance remain poorly characterized. There is currently a gap in our understanding of the physiological function of SGs during stress. Since there are only a few studies addressing SGs in planta, which are p...

Microalgal cultivation in photobioreactors and membrane separations are both considered sustainable processes. Here we explore their synergistic combination to extract and concentrate a heterologous sesquiterpenoid produced by engineered green algal cells. A hydrophobic hollow-fiber membrane contactor was used to allow interaction of culture broth...

Chlamydomonas reinhardtii has emerged as a powerful green cell factory for metabolic engineering of sustainable products created from the photosynthetic lifestyle of this microalga. Advances in nuclear genome modification and transgene expression are allowing robust engineering strategies to be demonstrated in this host. However, commonly used lab...

Microalga cultivation in photobioreactors and membrane separations are both considered sustainable processes. Here we explore their synergistic combination to extract and concentrate a heterologous sesquiterpenoid produced by engineered green algal cells. A hydrophobic hollow-fiber membrane contactor was used to allow interaction of culture broth a...

Chlamydomonas reinhardtii has emerged as a powerful green cell factory for metabolic engineering of sustainable products created from the photosynthetic lifestyle of this microalga. Advances in nuclear genome and transgene expression engineering are allowing robust engineering strategies to be demonstrated in this host. However, commonly used lab s...

Microbial production of heterologous metabolites is now a mature technology in many host organisms, opening new avenues for green production processes for specialty chemicals. At lab scale, petroleum-based hydrophobic bio-compatible solvents like dodecane can be used as a second phase on top of microbial cultures to act as a physical sink for heter...

Fatty acids are important biological components, yet the metabolism of fatty acids in microalgae is not clearly understood. Previous studies found that Chlamydomonas reinhardtii, the model microalga, incorporates exogenously added fatty acids but metabolizes them differently from animals and yeast. Furthermore, a recent metabolic flux analysis foun...

Microalgae have been widely recognized as promising hosts for production of various valuable compounds. However, low expression or silencing of transgenes in most microalgae species have hindered their broader implementation in biotechnological applications. In many eukaryotes, intron mediated enhancement (IME) of gene expression by inclusion of in...

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of guanosine triphosphate nucleotides. Among posttranslational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on the ER s...

Microalgae and cyanobacteria are photosynthetic microbes that can be grown with the simple inputs of water, carbon dioxide, (sun)light, and trace elements. Their engineering holds the promise of tailored bio-molecule production using sustainable, environmentally friendly waste carbon inputs. Although algal engineering examples are beginning to show...

Metabolic engineering of microbial hosts for the production of heterologous metabolites and biochemicals is an enabling technology to generate meaningful quantities of desired products that may be otherwise difficult to produce by traditional means. Heterologous metabolite production can be restricted by the accumulation of toxic products within th...

The EU Horizon2020 consortium PHOTOFUEL joined academic and industrial partners from biology, chemistry, engineering, engine design, and lifecycle assessment, making tremendous progress towards engine-ready fuels from CO2 via engineered photosynthetic microbes. Technical, environmental, economic, and societal opportunities and challenges were explo...

Livestock contributes to 14.5 percent of global greenhouse gas emissions, with ruminants being the largest contributor through enteric methane emissions. Although several mitigation strategies are available to reduce livestock methane, no consensus exists on which methods are the most effective. Here, the mitigation impact of the most pragmatic str...

Livestock contributes to 14.5 percent of global greenhouse gas emissions, with ruminants being the largest contributor through enteric methane emissions. Although several strategies are available to mitigate livestock methane, no consensus exists on which methods are the most effective. Here, we projected by 2050 the impact of the most pragmatic st...

Being integral primary producers in diverse ecosystems, microalgal genomes could be mined for ecological insights, but representative genome sequences are lacking for many phyla. We cultured and sequenced 107 microalgae species from 11 different phyla indigenous to varied geographies and climates. This collection was used to resolve genomic differe...

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of GTP nucleotides. Among post-translational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on ER structure remains uncle...

Efficient nuclear transgene expression in the green microalga Chlamydomonas reinhardtii is generally hindered by low transcription rates. Introns can increase transcript abundance by a process called Intron-Mediated Enhancement (IME) in this alga and has been broadly observed in other eukaryotes. However, the mechanisms of IME in microalgae are poo...

Despite global shifts in attitudes toward sustainability and increasing awareness of human impact on the environment, projected population growth and climate change require technological adaptations to ensure food and resource security at a global scale. Although desert areas have long been proposed as ideal sites for solar electricity generation,...

The green alga Chlamydomonas reinhardtii does not synthesize high-value ketocarotenoids like canthaxanthin and astaxanthin, however, a β-carotene ketolase (CrBKT) can be found in its genome. CrBKT is poorly expressed, contains a long C-terminal extension not found in homologues and likely represents a pseudogene in this alga. Here, we used syntheti...

Microalgae are rapidly growing, low-input requiring, sun light-utilizing microorganisms capable of converting carbon dioxide into various natural products, a major portion of which are hydrocarbons. Their cellular compartmentalization and photosynthetic apparatus depend on robust turnover of two hydrocarbon classes, isoprenoids and acyl-lipids. Thi...

The unicellular green microalga Chlamydomonas reinhardtii is a powerful photosyn‐ thetic model organism which is capable of heterotrophic growth on acetate as a sole carbon source. This capacity has enabled its use for investigations of perturba‐ tions in photosynthetic machinery as mutants can be recovered heterotrophically. Fixation of acetate...

The green alga Chlamydomonas reinhardtii does not synthesize high-value ketocarotenoids like canthaxanthin and astaxanthin, however, a β-carotene ketolase (CrBKT) can be found in its genome. CrBKT is poorly expressed, contains a long C-terminal extension not found in homologues and likely represents a pseudogene in this alga. Here, we used syntheti...

Main conclusions Eukaryotic microalgae hold incredible metabolic potential for the sustainable production of heterologous isoprenoid products. Recent advances in algal engineering have enabled the demonstration of prominent examples of heterologous isoprenoid production. Isoprenoids, also known as terpenes or terpenoids, are the largest class of...

Microalgae are regarded as promising organisms to develop innovative concepts based on their photosynthetic capacity that offers more sustainable production than heterotrophic hosts. However, to realize their potential as green cell factories, a major challenge is to make microalgae easier to engineer. A promising approach for rapid and predictable...

Liquid fuels sourced from fossil sources are the dominant energy form for mobile transport today. The consumption of fossil fuels is still increasing, resulting in a continued search for more sustainable methods to renew our supply of liquid fuel. Photosynthetic microorganisms naturally accumulate hydrocarbons that could serve as a replacement for...

Liquid fuels sourced from fossil sources are the dominant energy form for mobile transport today. The consumption of fossil fuels is still increasing, resulting in a continued search for more sustainable methods to renew our supply of liquid fuel. Photosynthetic microorganisms naturally accumulate hydrocarbons that could serve as a replacement for...

Photosynthetic microalgae harbor enormous potential as light-driven green-cell factories for sustainable bio-production of a range of natural and heterologous products such as isoprenoids. Their capacity for photosynthesis and rapid low-input growth with (sun)light and CO2 is coupled to a robust metabolic architecture structured toward the generati...

Currently, algal fuel research has commenced to shift towards genetically engineered mutants, able to express and excrete desired products directly into the culture. In this study, a mutant strain of Chlamydomonas reinhardtii, engineered for bisabolene (alternative biodiesel) excretion, was cultivated at different illumination and temperatures to i...

Among green freshwater microalgae, Chlamydomonas reinhardtii has the most comprehensive and developed molecular toolkit, however, advanced genetic and metabolic engineering driven from the nuclear genome is generally hindered by inherently low transgene expression levels. Progressive strain development and synthetic promoters have improved the capa...

Patchoulol is a sesquiterpene alcohol and an important natural product for the perfume industry. Corynebacterium glutamicum is the prominent host for the fermentative production of amino acids with an average annual production volume of ~6 million tons. Due to its robustness and well established large-scale fermentation, C. glutamicum has been engi...

Photosynthetic microbial hosts such as cyanobacteria and eukaryotic microalgae have recently emerged as alternative engineering platforms for the sustainable light-driven bio-production of terpenoids. Many desirable compounds with numerous applications can be produced in microorganisms by heterologous expression of terpene synthases. However, succe...

The heterologous expression of terpene synthases in microbial hosts has opened numerous possibilities for bioproduction of desirable metabolites. Photosynthetic microbial hosts present a sustainable alternative to traditional fermentative systems, using freely available (sun)light and carbon dioxide as inputs for bio-production. Here, we report the...

We present a versatile vector toolkit for nuclear transgene expression in the model green microalga Chlamydomonas reinhardtii. The vector was designed in a modular fashion which allows quick replacement of regulatory elements and genes of interest. The current toolkit comprises two antibiotic resistance markers (paromomycin and hygromycin B), five...

Microalgae are gaining importance as sustainable production hosts in the fields of biotechnology and bioenergy. A robust biomass accumulating strain of the genus Monoraphidium (SAG 48.87) was investigated in this work as a potential feedstock for biofuel production. The genome was sequenced, annotated, and key enzymes for triacylglycerol formation...

A Lolium perenne ice-binding protein (LpIBP) demonstrates superior ice recrystallization inhibition (IRI) activity and has proposed applications in cryopreservation, food texturing, as well as in being a "green" gas hydrate inhibitor. Recombinant production of LpIBP has been previously conducted in bacterial and yeast systems for studies of protein...