Engineering Yarrowia lipolytica to produce fuels and chemicals from xylose: A review

Sun, Tao; Yu, Yizi; Wang, Kaifeng; Ledesma-Amaro, Rodrigo; Ji, Xiao‐Jun

doi:10.1016/j.biortech.2021.125484

Cited by 39 publications

(21 citation statements)

References 69 publications

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“…There are some reports on glucose-based SA production but there is hardly any report on SA production from xylose by Y. lipolytica as yeast naturally cannot metabolize xylose, the second most abundant sugar after glucose . Therefore, xylose pathway was introduced into Y.…”

Section: Introductionmentioning

confidence: 99%

“…20 There are some reports on glucose-based SA production but there is hardly any report on SA production from xylose by Y. lipolytica as yeast naturally cannot metabolize xylose, the second most abundant sugar after glucose. 21 Therefore, xylose pathway was introduced into Y. lipolytica to enable SA production from xylose. 19 Moreover, it connects an independently developed pretreatment process with fermentation and downstream separation process.…”

Section: ■ Introductionmentioning

confidence: 99%

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Economic and Environmental Assessment of Succinic Acid Production from Sugarcane Bagasse

Shaji

Shastri

Kumar

et al. 2021

ACS Sustainable Chem. Eng.

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This work presents technoeconomic analysis (TEA) and life cycle assessment (LCA) of a novel biorefinery producing succinic acid (SA) from sugarcane bagasse. The process consists of acid pretreatment, fermentation, followed by downstream separation and purification. Experimental data for pretreatment and fermentation are adapted for a plant processing 4 t/h of dry bagasse, producing 405 kg/h of succinic acid with the same quantity of acetic acid as a side product. Downstream separation is simulated in ASPEN PLUS. The facility is assumed to be annexed to and heat-integrated with an existing sugar mill in India. LCA is performed considering cradle-to-gate scope with 1 kg of SA as the functional unit. The TEA results show that although the process is currently not economically feasible, expected improvements in fermentation yields will make it cost-competitive. For the expected yield, the product cost of SA is INR 121/kg ($1.61/kg), and the selling price of succinic acid should be INR 178/kg ($2.37/kg) for a payback period of 4 years. Pretreatment and fermentation are the biggest contributors to the product cost. The life cycle greenhouse gas (GHG) emissions are 1.39 kg of CO 2 equiv/kg succinic acid with electricity as the major contributor. Process improvement opportunities are identified to reduce the costs, as well as life cycle impacts.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Economic and Environmental Assessment of Succinic Acid Production from Sugarcane Bagasse

Shaji

Shastri

Kumar

et al. 2021

ACS Sustainable Chem. Eng.

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“…Xylose catabolism and overcoming catabolite repression are major boundaries to bioproduction on lignocellulosic biomass ( Sun et al, 2021 ). One study showed that carbon source switching enabled production of 20.6mg/L and 15.1mg/L limonene in Y. lipolytica from xylose and a 50% lignocellulosic biomass 50% YP rich medium broth, respectively ( Yao et al, 2020 ).…”

Section: Isoprenoid Production On Lignocellulosic Carbon Sourcesmentioning

confidence: 99%

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

Carruthers

Lee

2021

Front. Microbiol.

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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.

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“…Engineering metabolism for growth on non-native substrates (i.e., synthetic heterotrophy) has been an outstanding challenge for several decades in various microbial species ( 1–4 ). The traditional approach is to take a purely metabolic perspective and constitutively overexpression catabolic genes that input substrate to central carbon metabolism with the expectation that the native cellular systems can direct subsequent steps required for growth.…”

Section: Introductionmentioning

confidence: 99%

Integration of metabolism and regulation reveals rapid adaptability to growth on non-native substrates

Trivedi

Sullivan

Choudhury

et al. 2022

Preprint

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Engineering synthetic heterotrophy (i.e., growth on non-native substrates) is key to efficient bio-based valorization of various renewable (e.g., lignocellulosic biomass) and waste (e.g., plastics) substrates. Among these, engineering hemicellulosic pentose utilization has been well-explored in Saccharomyces cerevisiae (yeast) over several decades but genetic factors that constrain maximum growth rate remain elusive. Through a systematic analysis (flux balancing, directed evolution, functional genomics, and network modeling), we find that once global regulatory response is appropriately remodeled, wild-type-like growth profiles can be achieved with minimal metabolic engineering effort. This indicates that intrinsic yeast metabolism is highly adaptable to growth on non-native substrates. We identified that extrinsic factors – specifically, genes that direct flux of pentoses into central carbon metabolism – are rate limiting. We also find that deletion of endogenous genes to promote growth demonstrate inconsistent outcomes that are genetic-context- and condition-dependent. For the most part, these knockouts also lead to deleterious pleiotropic effects that decrease the robustness of strains against inhibitors commonly found in lignocellulosic hydrolysate. Thus, perturbation of intrinsic factors (e.g., metabolic, regulatory genes) provides incremental and inconsistent benefits at best and at worst, is detrimental. Not only do the findings and approach described here expedite the design-build-test cycle but also simplifies the engineering process. Overall, this work provides insight into the limitations and pitfalls to realizing efficient synthetic heterotrophy and provides a novel paradigm to engineer the same.

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Engineering Yarrowia lipolytica to produce fuels and chemicals from xylose: A review

Cited by 39 publications

References 69 publications

Economic and Environmental Assessment of Succinic Acid Production from Sugarcane Bagasse

Economic and Environmental Assessment of Succinic Acid Production from Sugarcane Bagasse

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

Integration of metabolism and regulation reveals rapid adaptability to growth on non-native substrates

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