Metabolic engineering a yeast to produce astaxanthin

Lin, Yu‐Ju; Chang, Jui-Jen; Lin, Hao-Yeh; Thia, Caroline; Kao, Yi-Ying; Huang, Chieh-Chen; Li, Wen-Hsiung

doi:10.1016/j.biortech.2017.07.116

Cited by 59 publications

(38 citation statements)

References 30 publications

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“…The amounts of carotenoids produced by the production strain constructed in this study are equivalent to the first production strain engineered in yeast [ 52 ]. Recent advances in manipulating metabolic pathways and genetic elements have increased the production in baker’s yeast [ 8 , 30 ], and similar approaches could be undertaken to increase production in A. nidulans .…”

Section: Discussionmentioning

confidence: 99%

CoIN: co-inducible nitrate expression system for secondary metabolites in Aspergillus nidulans

Wiemann

Soukup

Folz

et al. 2018

Fungal Biol Biotechnol

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BackgroundSequencing of fungal species has demonstrated the existence of thousands of putative secondary metabolite gene clusters, the majority of them harboring a unique set of genes thought to participate in production of distinct small molecules. Despite the ready identification of key enzymes and potential cluster genes by bioinformatics techniques in sequenced genomes, the expression and identification of fungal secondary metabolites in the native host is often hampered as the genes might not be expressed under laboratory conditions and the species might not be amenable to genetic manipulation. To overcome these restrictions, we developed an inducible expression system in the genetic model Aspergillus nidulans.ResultsWe genetically engineered a strain of A. nidulans devoid of producing eight of the most abundant endogenous secondary metabolites to express the sterigmatocystin Zn(II)2Cys6 transcription factor-encoding gene aflR and its cofactor aflS under control of the nitrate inducible niiA/niaD promoter. Furthermore, we identified a subset of promoters from the sterigmatocystin gene cluster that are under nitrate-inducible AflR/S control in our production strain in order to yield coordinated expression without the risks from reusing a single inducible promoter. As proof of concept, we used this system to produce β-carotene from the carotenoid gene cluster of Fusarium fujikuroi.ConclusionUtilizing one-step yeast recombinational cloning, we developed an inducible expression system in the genetic model A. nidulans and show that it can be successfully used to produce commercially valuable metabolites.Electronic supplementary materialThe online version of this article (10.1186/s40694-018-0049-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

CoIN: co-inducible nitrate expression system for secondary metabolites in Aspergillus nidulans

Wiemann

Soukup

Folz

et al. 2018

Fungal Biol Biotechnol

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“…Biosynthesis of Carotenoids and Apocarotenoids by Microorganisms and Their Industrial Potential http://dx.doi.org/10.5772/intechopen.79061 bkt) into the Yarrowia lipolytica. As a result, they were able to achieve about 9.97 mg/g DCW of astaxanthin [70]. By developing and using an efficient multidimensional heuristic process and colorimetric medium screening approach, our laboratory has achieved one of the best results of astaxanthin using E. coli, 320 mg/L and 15 mg/g DCW [71].…”

Section: Progress In Carotenoid Researchmentioning

confidence: 98%

“…By developing and using an efficient multidimensional heuristic process and colorimetric medium screening approach, our laboratory has achieved one of the best results of astaxanthin using E. coli, 320 mg/L and 15 mg/g DCW [71]. As summarized in Table 2, the engineered S. cerevisiae [69], Y. lipolytica [66], Kluyveromyces marxianus [70] and E. coli [71] have produced promisingly high titers and yields of astaxanthin. The recently achieved titers and yields [66,70,71] are from 10-fold to 100-fold higher than those previously reported in S. cerevisiae [72,73], E. coli [74,75], Corynebacterium glutamicum [76] and Xanthophyllomyces dendrorhous, previously as Phaffia rhodozyma [77][78][79].…”

Section: Progress In Carotenoid Researchmentioning

confidence: 99%

Biosynthesis of Carotenoids and Apocarotenoids by Microorganisms and Their Industrial Potential

Zhang¹

2018

Progress in Carotenoid Research

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Carotenoids are a large group of natural pigments, ranging from red, to orange, to yellow colors. Synthesized by plants and some microorganisms (e.g., microalgae, fungi and bacteria), carotenoids have important physiological functions (e.g., light harvesting). Apocarotenoids are carotenoid-derived compounds and play important roles in various biological activities (e.g., plant hormones). Many carotenoids and apocarotenoids have high economic value in feed, food, supplements, cosmetics and pharmaceutical industries. Despite high commercial values, they are severely undersupplied because of low abundance in natural hosts (usually a few milligrams per kilogram of raw materials). Furthermore, plants or microbes usually produce mixtures of these molecules with very similar physical and chemical properties (such as α-and β-carotenes). All these features render the extraction from natural hosts rather difficult and also very costly both from process economics and sustainable land-use viewpoints. Chemical synthesis is also expensive due to structural complexity (e.g., astaxanthin has many unsaturated bonds and two chiral regions). Biotechnology via the rapidly advancing metabolic engineering and synthetic biology approaches has led to alternative ways to attain several carotenoids and apocarotenoids at relatively high titers and yields using fast-growing microorganisms. This chapter briefly reviews the biosynthesis of carotenoids and apocarotenoids by microorganisms and their industrial potential.

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“…marxianus is also distinguished by its thermotolerance [36,87] and the highest growth rate in eukaryotes [88]. In recent years, interest also increased in several new applications such as production of biomolecules [89,90], biocatalysts [91,92], and heterologous protein expression [93,94].…”

Section: Complete Genome Sequence Of Thermotolerant Yeast K Marxianumentioning

confidence: 99%

Potential of Thermotolerant Ethanologenic Yeasts Isolated from ASEAN Countries and Their Application in High- Temperature Fermentation

Kosaka¹,

Lertwattanasakul²,

NadchanokRodrussamee³

et al. 2019

Fuel Ethanol Production From Sugarcane

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Thermotolerant ethanologenic yeasts receive attention as alternative bio-ethanol producers to traditionally used yeast, Saccharomyces cerevisiae. Their utilization is expected to provide several benefits for bio-ethanol production due to their characteristics and robustness. They have been isolated from a wide variety of environments in a number of ASEAN countries: Thailand, Vietnam, Laos, and Indonesia. One of these yeasts, Kluyveromyces marxianus has been investigated regarding characteristics. Some strains efficiently utilize xylose, which is a main component of the 2nd generation biomass. In addition, the genetic basis of K. marxianus has been revealed by genomic sequencing and is exploited for further improvement of the strains by thermal adaptation or gene engineering techniques. Moreover, the glucose repression of K. marxianus and its mechanisms has been investigated. Results suggest that K. marxianus is an alternative to S. cerevisiae in next-generation bio-ethanol production industry. Indeed, we have succeeded to apply K. marxianus for bio-ethanol production in a newly developed process, which combines high-temperature fermentation with simultaneous fermentation and distillation under low pressure. This chapter aims to provide valuable information on thermotolerant ethanologenic yeasts and their application, which may direct the economic bioproduction of ethanol and other useful materials in the future.Recently, thermotolerant microorganisms were found among mesophiles with optimum growth temperatures that are 5-10°C higher than those of the typical mesophilic strains Fuel Ethanol Production from Sugarcane 122 Potential of Thermotolerant Ethanologenic Yeasts Isolated from ASEAN Countries… http://dx.doi.org/10.5772/intechopen.79144 123Recently, there have been several reports on ethanol production at high temperatures using P. kudriavzevii (formerly known as I. orientalis). Several P. kudriavzevii strains were reported to grow and produce high levels of ethanol at high temperatures. The strain DMKU 3-ET15 was isolated from traditional fermented pork sausage in Thailand by an enrichment technique in a medium supplemented with 4% ethanol at 40°C. The strain produced 78.6 g/L ethanol from 180 g/L glucose at 40°C [20]. The strain KVMP10 that was isolated from soil located beneath apple trees for ethanol production from orange peel achieved 54 g/L ethanol at 42°C [48]. Strain RZ8-1 that was recently isolated from various samples collected from plant orchards in Thailand produced 33.8 g/L ethanol from 160 g/L glucose at 40°C [49].

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Metabolic engineering a yeast to produce astaxanthin

Cited by 59 publications

References 30 publications

CoIN: co-inducible nitrate expression system for secondary metabolites in Aspergillus nidulans

CoIN: co-inducible nitrate expression system for secondary metabolites in Aspergillus nidulans

Biosynthesis of Carotenoids and Apocarotenoids by Microorganisms and Their Industrial Potential

Potential of Thermotolerant Ethanologenic Yeasts Isolated from ASEAN Countries and Their Application in High- Temperature Fermentation

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