Model-based biotechnological potential analysis of <i>Kluyveromyces marxianus</i> central metabolism

Pentjuss, Agris; Stalidzāns, Egils; Liepiņš, Jānis; Kokina, Agnese; Martynova, Jekaterina; Zikmanis, Pēteris; Mozga, Ivars; Scherbaka, Rita; Hartman, Hassan; Poolman, Mark G.; Fell, David A.; Vigants, Armands

doi:10.1007/s10295-017-1946-8

Cited by 40 publications

(21 citation statements)

References 105 publications

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“…Increased biomass accumulation in xylose media relative to glucose is thought to be related to phosphoketolase activity (Evans & Ratledge, ). Recent metabolic models of K. marxianus also show xylose to be a promising substrate, especially after adjusting enzyme cofactor preferences and activity in the xylose reductase step (Pentjuss et al, ). This organism's unique metabolism and ability to assimilate a wide range of substrates makes it a promising host for the synthesis of acetyl‐CoA based products such as polyketides.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus

McTaggart

Bever

Bassett

et al. 2019

Biotech & Bioengineering

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Kluyveromyces marxianus is a promising nonconventional yeast for biobased chemical production due to its rapid growth rate, high TCA cycle flux, and tolerance to low pH and high temperature. Unlike Saccharomyces cerevisiae, K. marxianus grows on low-cost substrates to cell densities that equal or surpass densities in glucose, which can be beneficial for utilization of lignocellulosic biomass (xylose), biofuel production waste (glycerol), and whey (lactose). We have evaluated K. marxianus for the synthesis of polyketides, using triacetic acid lactone (TAL) as the product. The 2-pyrone synthase (2-PS) was expressed on a CEN/ARS plasmid in three different strains, and the effects of temperature, carbon source, and cultivation strategy on TAL levels were determined.The highest titer was obtained in defined 1% xylose medium at 37°C, with substantial titers at 41 and 43°C. The introduction of a high-stability 2-PS mutant and a promoter substitution increased titer four-fold. 2-PS expression from a multi-copy pKD1-based plasmid improved TAL titers a further five-fold. Combining the best plasmid, promoter, and strain resulted in a TAL titer of 1.24 g/L and a yield of 0.0295 mol TAL/mol carbon for this otherwise unengineered strain in 3 ml tube culture. This is an excellent titer and yield (on xylose) before metabolic engineering or fed-batch culture relative to other hosts (on glucose), and demonstrates the promise of this rapidly growing and thermotolerant yeast species for polyketide production.

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Section: Introductionmentioning

confidence: 99%

Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus

McTaggart

Bever

Bassett

et al. 2019

Biotech & Bioengineering

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“…Nevertheless, the bacterial strain Z. mobilis DSM 3580 had a clearly lower (p < 0.05) sugar consumption, which could be related to its limited carbohydrate utilisation (Table 3). According to metabolic stoichiometry, 1 mol of glucose produces 2 mol of ethanol, and 1 mol of xylose produces 1.6 mol of ethanol (or even 0.96 mol ethanol) (Pentjuss et al, 2017). This implies theoretical ethanol yields (YE) of 0.511 g/g for glucose and 0.294-0.491 g/g for xylose.…”

Section: Ethanol Production From Tomato Wastementioning

confidence: 99%

Tomato Waste from Processing Industries as a Feedstock for Biofuel Production

et al. 2019

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Tomato pomace, a solid by-product of tomato processing industries, was assessed for the first time as a feedstock for acetone-butanol-ethanol-isopropanol (ABEI) fermentation. After pretreatment with autohydrolysis and enzymatic hydrolysis, a broth containing 44.1 g/L total sugars was obtained. Twelve Clostridium strains were compared to find an appropriate microorganism for the transformation of tomato pomace hydrolysate. C. acetobutylicum DSM 792 produced 6.20 ± 0.63 g/L butanol and 8.28 ± 0.85 g/L isopropanol, whereas C. beijerinckii DSM 6423 produced 6.52 ± 0.17 g/L butanol and 7.30 ± 0.23 g/L isopropanol. In addition, another hydrolysate with a higher total sugar content (85.1 g/L) was prepared and employed for bioethanol production by comparing twelve different yeast and bacterial strains. Kluyveromyces marxianus DSM 5422, Saccharomyces cerevisiae Ethanol Red ® , S. cerevisiae Hércules and Lachancea thermotolerans DSM 3434 produced 20.1-21.7 g/L ethanol. According to these results, tomato pomace could be an interesting feedstock for ABEI biorefineries.

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“…Stoichiometric models have been applied at genome scale for many organisms including Saccharomyces cerevisiae [ 8 ], Escherichia coli [ 9 ], and human [ 10 ]. Stoichiometric models are useful also at a smaller scale, for instance, concentrating on central carbon metabolism [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Model-based metabolism design: constraints for kinetic and stoichiometric models

Stalidzāns

Seiman

Peebo

et al. 2018

Biochemical Society Transactions

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The implementation of model-based designs in metabolic engineering and synthetic biology may fail. One of the reasons for this failure is that only a part of the real-world complexity is included in models. Still, some knowledge can be simplified and taken into account in the form of optimization constraints to improve the feasibility of model-based designs of metabolic pathways in organisms. Some constraints (mass balance, energy balance, and steady-state assumption) serve as a basis for many modelling approaches. There are others (total enzyme activity constraint and homeostatic constraint) proposed decades ago, but which are frequently ignored in design development. Several new approaches of cellular analysis have made possible the application of constraints like cell size, surface, and resource balance. Constraints for kinetic and stoichiometric models are grouped according to their applicability preconditions in (1) general constraints, (2) organism-level constraints, and (3) experiment-level constraints. General constraints are universal and are applicable for any system. Organism-level constraints are applicable for biological systems and usually are organism-specific, but these constraints can be applied without information about experimental conditions. To apply experimental-level constraints, peculiarities of the organism and the experimental set-up have to be taken into account to calculate the values of constraints. The limitations of applicability of particular constraints for kinetic and stoichiometric models are addressed.

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Model-based biotechnological potential analysis of Kluyveromyces marxianus central metabolism

Cited by 40 publications

References 105 publications

Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus

Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus

Tomato Waste from Processing Industries as a Feedstock for Biofuel Production

Model-based metabolism design: constraints for kinetic and stoichiometric models

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