Metabolic engineering of the non-conventional yeast Pichia ciferrii for production of rare sphingoid bases

Börgel, Daniel; Berg, Marco van den; Hüller, Thomas; Andrea, Heiko; Liebisch, Gerhard; Boles, Eckhard; Schorsch, Christoph; Pol, Ruud van der; Arink, Anne; Boogers, Ilco; Hoeven, Rob van der; Korevaar, Kees; Farwick, Mike; Köhler, Tim; Schaffer, Steffen

doi:10.1016/j.ymben.2012.03.003

Cited by 24 publications

(13 citation statements)

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“…The existence of sphingolipid metabolism genes is in accordance with recent studies (4,15). Due to the ability of W. ciferrii NRRL Y-1031 F-60-10 to secrete acetylated sphingoid bases, protein sequences were screened for Rsb1p-like sequences using BLASTp (1).…”

Section: T He Ascomycetous Yeast Wickerhamomyces Ciferrii (Synonymsupporting

confidence: 53%

“…Therefore, these sphingolipids are valuable active ingredients used for pharmaceutical and cosmetic applications (5,7). W. ciferrii is already used industrially for fermentative production of tetraacetyl phytosphingosine (TAPS), and metabolic engineering methods are available (2,4,15,16).…”

Section: T He Ascomycetous Yeast Wickerhamomyces Ciferrii (Synonymmentioning

confidence: 99%

“…These Rsb1p-like sequences might contribute to the export of sphingolipid derivatives. Beyond the fundamental knowledge that has been established for W. ciferrii NRRL Y-1031 F-60-10, the draft genome presents a basis for the identification of target genes contributing to further improvement of sphingoid base production by metabolic engineering as presented in recent studies (4,15).…”

Section: T He Ascomycetous Yeast Wickerhamomyces Ciferrii (Synonymmentioning

confidence: 99%

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Draft Genome Sequence of Wickerhamomyces ciferrii NRRL Y-1031 F-60-10

et al. 2012

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Wickerhamomyces ciferrii is a microorganism characterized by the production and secretion of large amounts of acetylated sphingoid bases, in particular tetraacetyl phytosphingosine. Here, we present the 15.90-Mbp draft genome sequence of W. ciferrii NRRL Y-1031 F-60-10 generated by pyrosequencing and de novo assembly. The draft genome sequence comprising 364 contigs in 150 scaffolds was annotated and covered 6,702 protein-coding sequences. This information will contribute to the metabolic engineering of this yeast to improve the yield and spectrum of acetylated sphingoid bases in biotechnological production.

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Section: T He Ascomycetous Yeast Wickerhamomyces Ciferrii (Synonymsupporting

confidence: 53%

Section: T He Ascomycetous Yeast Wickerhamomyces Ciferrii (Synonymmentioning

confidence: 99%

Section: T He Ascomycetous Yeast Wickerhamomyces Ciferrii (Synonymmentioning

confidence: 99%

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Draft Genome Sequence of Wickerhamomyces ciferrii NRRL Y-1031 F-60-10

et al. 2012

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“…Thus, metabolic engineering strategies including the implementation and improvement of a metabolic pathway for the conversion of sphinganine to sphingosine were used to develop a final strain capable of producing approximately 240 mg.L -1 triacetylated sphingosine (TriASo) in shake flasks and up to 890 mg. kg -1 in lab-scale fermentation. Further improvement of such strain could lead to even higher concentrations of sphinganine and sphingosine for cosmetic and pharmaceutical applications [30]. These results are still preliminary for industrial application, but they clearly demonstrate the potential of bioprospecting for developing bioprocesses.…”

Section: ]mentioning

confidence: 79%

Genetic improvement of microorganisms for applications in biorefineries

Paes

Almeida

2014

Chem. Biol. Technol. Agric.

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The development of biorefineries directed to the production of fuels, chemicals and energy is important to reduce economic dependence and environmental impacts of a petroleum-based economy. Microorganisms are essential in several industrial bioprocesses nowadays, and it is expected that new microbial bioprocesses will play a key role in biorefineries. However, the bioconversion process requires a robust and highly productive microorganism. In this scenario, several strategies to genetically improve microorganisms to overcome the bioprocesses challenges have been considered. In this work, we review microorganisms importance in the biorefineries concept, highlight the desirable traits they must hold in order to be employed, and discuss the main strategies to improve such traits. The focuses of this work are on four main targets in the improvement of microorganisms: driving carbon flux towards the desired pathway, increasing tolerance to toxic compounds, increasing substrate uptake range and new products generation.

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“…Sphingolipids are a class of lipids containing a long-chain base (LCB) backbone (known as a sphingoid base) and are essential components of eukaryotic cellular membranes ( Gault et al, 2010 ; Börgel et al, 2012 ; Singh and Del Poeta, 2016 ). The simple structures of LCBs, including those of sphingosine, dihydrosphingosine, and phytosphingosine, form diverse sphingolipids via modifications such as phosphorylation or acylation.…”

Section: Introductionmentioning

confidence: 99%

Differences in the Fatty Acid Profile, Morphology, and Tetraacetylphytosphingosine-Forming Capability Between Wild-Type and Mutant Wickerhamomyces ciferrii

Choi

Hwang

Cho

et al. 2021

Front. Bioeng. Biotechnol.

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One tetraacetylphytosphingosine (TAPS)-producing Wickerhamomyces ciferrii mutant was obtained by exposing wild-type W. ciferrii to γ-ray irradiation. The mutant named 736 produced up to 9.1 g/L of TAPS (218.7 mg-TAPS/g-DCW) during batch fermentation in comparison with 1.7 g/L of TAPS (52.2 mg-TAPS/g-DCW) for the wild type. The highest production, 17.7 g/L of TAPS (259.6 mg-TAPS/g-DCW), was obtained during fed-batch fermentation by mutant 736. Fatty acid (FA) analysis revealed an altered cellular FA profile of mutant 736: decrease in C16:0 and C16:1 FA levels, and increase in C18:1 and C18:2 FA levels. Although a significant change in the cellular FA profile was observed, scanning electron micrographs showed that morphology of wild-type and mutant 736 cells was similar. Genetic alteration analysis of eight TAPS biosynthesis-related genes revealed that there are no mutations in these genes in mutant 736; however, mRNA expression analysis indicated 30% higher mRNA expression of TCS10 among the eight genes in mutant 736 than that in the wild-type. Collectively, these results imply that the enhancement of TAPS biosynthesis in mutant 736 may be a consequence of system-level genetic and physiological alterations of a complicated metabolic network. Reverse metabolic engineering based on system-level omics analysis of mutant 736 can make the mutant more suitable for commercial production of TAPS.

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Metabolic engineering of the non-conventional yeast Pichia ciferrii for production of rare sphingoid bases

Cited by 24 publications

References 74 publications

Draft Genome Sequence of Wickerhamomyces ciferrii NRRL Y-1031 F-60-10

Draft Genome Sequence of Wickerhamomyces ciferrii NRRL Y-1031 F-60-10

Genetic improvement of microorganisms for applications in biorefineries

Differences in the Fatty Acid Profile, Morphology, and Tetraacetylphytosphingosine-Forming Capability Between Wild-Type and Mutant Wickerhamomyces ciferrii

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