Engineering de novo anthocyanin production in Saccharomyces cerevisiae View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-07-03

AUTHORS

Mark Levisson, Constantinos Patinios, Sascha Hein, Philip A. de Groot, Jean-Marc Daran, Robert D. Hall, Stefan Martens, Jules Beekwilder

ABSTRACT

BACKGROUND: Anthocyanins are polyphenolic pigments which provide pink to blue colours in fruits and flowers. There is an increasing demand for anthocyanins, as food colorants and as health-promoting substances. Plant production of anthocyanins is often seasonal and cannot always meet demand due to low productivity and the complexity of the plant extracts. Therefore, a system of on-demand supply is useful. While a number of other (simpler) plant polyphenols have been successfully produced in the yeast Saccharomyces cerevisiae, production of anthocyanins has not yet been reported. RESULTS: Saccharomyces cerevisiae was engineered to produce pelargonidin 3-O-glucoside starting from glucose. Specific anthocyanin biosynthetic genes from Arabidopsis thaliana and Gerbera hybrida were introduced in a S. cerevisiae strain producing naringenin, the flavonoid precursor of anthocyanins. Upon culturing, pelargonidin and its 3-O-glucoside were detected inside the yeast cells, albeit at low concentrations. A number of related intermediates and side-products were much more abundant and were secreted into the culture medium. To optimize titers of pelargonidin 3-O-glucoside further, biosynthetic genes were stably integrated into the yeast genome, and formation of a major side-product, phloretic acid, was prevented by engineering the yeast chassis. Further engineering, by removing two glucosidases which are known to degrade pelargonidin 3-O-glucoside, did not result in higher yields of glycosylated pelargonidin. In aerated, pH controlled batch reactors, intracellular pelargonidin accumulation reached 0.01 µmol/gCDW, while kaempferol and dihydrokaempferol were effectively exported to reach extracellular concentration of 20 µM [5 mg/L] and 150 µM [44 mg/L], respectively. CONCLUSION: The results reported in this study demonstrate the proof-of-concept that S. cerevisiae is capable of de novo production of the anthocyanin pelargonidin 3-O-glucoside. Furthermore, while current conversion efficiencies are low, a number of clear bottlenecks have already been identified which, when overcome, have huge potential to enhance anthocyanin production efficiency. These results bode very well for the development of fermentation-based production systems for specific and individual anthocyanin molecules. Such systems have both great scientific value for identifying and characterising anthocyanin decorating enzymes as well as significant commercial potential for the production of, on-demand, pure bioactive compounds to be used in the food, health and even pharma industries. More... »

PAGES

103

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12934-018-0951-6

DOI

http://dx.doi.org/10.1186/s12934-018-0951-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105300894

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29970082


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29 schema:description BACKGROUND: Anthocyanins are polyphenolic pigments which provide pink to blue colours in fruits and flowers. There is an increasing demand for anthocyanins, as food colorants and as health-promoting substances. Plant production of anthocyanins is often seasonal and cannot always meet demand due to low productivity and the complexity of the plant extracts. Therefore, a system of on-demand supply is useful. While a number of other (simpler) plant polyphenols have been successfully produced in the yeast Saccharomyces cerevisiae, production of anthocyanins has not yet been reported. RESULTS: Saccharomyces cerevisiae was engineered to produce pelargonidin 3-O-glucoside starting from glucose. Specific anthocyanin biosynthetic genes from Arabidopsis thaliana and Gerbera hybrida were introduced in a S. cerevisiae strain producing naringenin, the flavonoid precursor of anthocyanins. Upon culturing, pelargonidin and its 3-O-glucoside were detected inside the yeast cells, albeit at low concentrations. A number of related intermediates and side-products were much more abundant and were secreted into the culture medium. To optimize titers of pelargonidin 3-O-glucoside further, biosynthetic genes were stably integrated into the yeast genome, and formation of a major side-product, phloretic acid, was prevented by engineering the yeast chassis. Further engineering, by removing two glucosidases which are known to degrade pelargonidin 3-O-glucoside, did not result in higher yields of glycosylated pelargonidin. In aerated, pH controlled batch reactors, intracellular pelargonidin accumulation reached 0.01 µmol/g<sub>CDW</sub>, while kaempferol and dihydrokaempferol were effectively exported to reach extracellular concentration of 20 µM [5 mg/L] and 150 µM [44 mg/L], respectively. CONCLUSION: The results reported in this study demonstrate the proof-of-concept that S. cerevisiae is capable of de novo production of the anthocyanin pelargonidin 3-O-glucoside. Furthermore, while current conversion efficiencies are low, a number of clear bottlenecks have already been identified which, when overcome, have huge potential to enhance anthocyanin production efficiency. These results bode very well for the development of fermentation-based production systems for specific and individual anthocyanin molecules. Such systems have both great scientific value for identifying and characterising anthocyanin decorating enzymes as well as significant commercial potential for the production of, on-demand, pure bioactive compounds to be used in the food, health and even pharma industries.
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37 Engineering de novo anthocyanin production
38 Gerbera hybrida
39 Saccharomyces
40 Saccharomyces cerevisiae
41 Specific anthocyanin biosynthetic genes
42 accumulation
43 acid
44 anthocyanin biosynthetic genes
45 anthocyanin molecules
46 anthocyanin pelargonidin 3
47 anthocyanin production
48 anthocyanin production efficiency
49 anthocyanins
50 batch reactor
51 bioactive compounds
52 biosynthetic genes
53 blue color
54 bottleneck
55 cells
56 cerevisiae
57 cerevisiae strain
58 chassis
59 clear bottleneck
60 color
61 colorants
62 commercial potential
63 complexity
64 compounds
65 concentration
66 concept
67 conversion efficiency
68 culture medium
69 current conversion efficiency
70 de novo anthocyanin production
71 de novo production
72 demand
73 demand supply
74 development
75 dihydrokaempferol
76 efficiency
77 engineering
78 enzyme
79 extracellular concentration
80 extract
81 fermentation-based production systems
82 flavonoid precursors
83 flowers
84 food
85 food colorants
86 formation
87 fruit
88 further engineering
89 genes
90 genome
91 glucose
92 glucosidases
93 glucoside
94 great scientific value
95 health
96 health-promoting substances
97 high yield
98 huge potential
99 hybrida
100 individual anthocyanin molecules
101 industry
102 intermediates
103 intracellular pelargonidin accumulation
104 kaempferol
105 low concentrations
106 low productivity
107 medium
108 molecules
109 naringenin
110 novo anthocyanin production
111 novo production
112 number
113 pelargonidin
114 pelargonidin 3
115 pelargonidin accumulation
116 phloretic acid
117 pigments
118 plant extracts
119 plant polyphenols
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124 precursors
125 production
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128 production systems
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130 proof
131 pure bioactive compounds
132 reactor
133 related intermediates
134 results
135 scientific value
136 significant commercial potential
137 strains
138 study
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141 such systems
142 supply
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144 thaliana
145 titers
146 values
147 yeast Saccharomyces
148 yeast cells
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150 yeast genome
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