Carnosic acid production from sugarcane syrup by engineered yeast in fed-batch fermentation

Erdem Carsanba; Sara Fernandes; Felipe Beato; Luís Carlos Carvalho; Ana Pintado; Ana Lopes; Mónica Ribeiro; Tânia Leal; Manuela Pintado; Carla Oliveira

doi:10.3390/fermentation11030147

Carnosic acid production from sugarcane syrup by engineered yeast in fed-batch fermentation

Erdem Carsanba, Sara Fernandes, Felipe Beato, Luís Carlos Carvalho, Ana Pintado, Ana Lopes, Mónica Ribeiro, Tânia Leal, Manuela Pintado, Carla Oliveira^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Phenolic diterpene carnosic acid (CA) is widely used in the food, nutritional health, and cosmetic industries due to its antioxidative and antimicrobial properties. This work aimed to overproduce CA in Saccharomyces cerevisiae from sugarcane syrup in fed-batch 2 L bioreactor fermentation. A geranylgeranyl diphosphate (GGPP)-producing strain modified with genes encoding the enzymes copalyl diphosphate synthase (Pv.CPS), miltiradiene synthase (Ro.KSL2), hydroxy ferruginol synthase (Ro.HFS), CA synthase (Ro.CYP76AK8), CYP reductase (At.ATR1), and transketolase (TKL1) was used. Lowering the feed rate from 12–26 g/L/h to 7–8 g/L/h, and the use of a dynamic dissolved oxygen (DO) trigger (min. 10%, max. 40%, threshold 70%) instead of a DO trigger of 30%, enhanced CA production by 27%. As a result, the highest CA titer ever reported to date, 191.4 mg/L, was obtained in 4-day fermentation. This study shows the feasibility of engineered yeast to produce CA from the sustainable feedstock sugarcane syrup.

Original language	English
Article number	147
Number of pages	11
Journal	Fermentation
Volume	11
Issue number	3
DOIs	https://doi.org/10.3390/fermentation11030147
Publication status	Published - 15 Mar 2025

Keywords

Carnosic acid
Dynamic dissolved oxygen trigger
Engineered Saccharomyces cerevisiae
Fed-batch fermentation
Sugarcane syrup

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/fermentation11030147Licence: CC BY

117268586Final published version, 3.75 MBLicence: CC BY

http://hdl.handle.net/10400.14/52968Licence: CC BY

Cite this

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title = "Carnosic acid production from sugarcane syrup by engineered yeast in fed-batch fermentation",

abstract = "Phenolic diterpene carnosic acid (CA) is widely used in the food, nutritional health, and cosmetic industries due to its antioxidative and antimicrobial properties. This work aimed to overproduce CA in Saccharomyces cerevisiae from sugarcane syrup in fed-batch 2 L bioreactor fermentation. A geranylgeranyl diphosphate (GGPP)-producing strain modified with genes encoding the enzymes copalyl diphosphate synthase (Pv.CPS), miltiradiene synthase (Ro.KSL2), hydroxy ferruginol synthase (Ro.HFS), CA synthase (Ro.CYP76AK8), CYP reductase (At.ATR1), and transketolase (TKL1) was used. Lowering the feed rate from 12–26 g/L/h to 7–8 g/L/h, and the use of a dynamic dissolved oxygen (DO) trigger (min. 10\%, max. 40\%, threshold 70\%) instead of a DO trigger of 30\%, enhanced CA production by 27\%. As a result, the highest CA titer ever reported to date, 191.4 mg/L, was obtained in 4-day fermentation. This study shows the feasibility of engineered yeast to produce CA from the sustainable feedstock sugarcane syrup.",

keywords = "Carnosic acid, Dynamic dissolved oxygen trigger, Engineered Saccharomyces cerevisiae, Fed-batch fermentation, Sugarcane syrup",

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AU - Carsanba, Erdem

AU - Fernandes, Sara

AU - Beato, Felipe

AU - Carvalho, Luís Carlos

AU - Pintado, Ana

AU - Lopes, Ana

AU - Ribeiro, Mónica

AU - Leal, Tânia

AU - Pintado, Manuela

AU - Oliveira, Carla

PY - 2025/3/15

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N2 - Phenolic diterpene carnosic acid (CA) is widely used in the food, nutritional health, and cosmetic industries due to its antioxidative and antimicrobial properties. This work aimed to overproduce CA in Saccharomyces cerevisiae from sugarcane syrup in fed-batch 2 L bioreactor fermentation. A geranylgeranyl diphosphate (GGPP)-producing strain modified with genes encoding the enzymes copalyl diphosphate synthase (Pv.CPS), miltiradiene synthase (Ro.KSL2), hydroxy ferruginol synthase (Ro.HFS), CA synthase (Ro.CYP76AK8), CYP reductase (At.ATR1), and transketolase (TKL1) was used. Lowering the feed rate from 12–26 g/L/h to 7–8 g/L/h, and the use of a dynamic dissolved oxygen (DO) trigger (min. 10%, max. 40%, threshold 70%) instead of a DO trigger of 30%, enhanced CA production by 27%. As a result, the highest CA titer ever reported to date, 191.4 mg/L, was obtained in 4-day fermentation. This study shows the feasibility of engineered yeast to produce CA from the sustainable feedstock sugarcane syrup.

AB - Phenolic diterpene carnosic acid (CA) is widely used in the food, nutritional health, and cosmetic industries due to its antioxidative and antimicrobial properties. This work aimed to overproduce CA in Saccharomyces cerevisiae from sugarcane syrup in fed-batch 2 L bioreactor fermentation. A geranylgeranyl diphosphate (GGPP)-producing strain modified with genes encoding the enzymes copalyl diphosphate synthase (Pv.CPS), miltiradiene synthase (Ro.KSL2), hydroxy ferruginol synthase (Ro.HFS), CA synthase (Ro.CYP76AK8), CYP reductase (At.ATR1), and transketolase (TKL1) was used. Lowering the feed rate from 12–26 g/L/h to 7–8 g/L/h, and the use of a dynamic dissolved oxygen (DO) trigger (min. 10%, max. 40%, threshold 70%) instead of a DO trigger of 30%, enhanced CA production by 27%. As a result, the highest CA titer ever reported to date, 191.4 mg/L, was obtained in 4-day fermentation. This study shows the feasibility of engineered yeast to produce CA from the sustainable feedstock sugarcane syrup.

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KW - Dynamic dissolved oxygen trigger

KW - Engineered Saccharomyces cerevisiae

KW - Fed-batch fermentation

KW - Sugarcane syrup

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Carnosic acid production from sugarcane syrup by engineered yeast in fed-batch fermentation

Abstract

Keywords

UN SDGs

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ALCHEMY: Capturing High Value from Industrial Fermentation BioProducts

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Carnosic acid production from sugarcane syrup by engineered yeast in fed-batch fermentation

Abstract

Keywords

UN SDGs

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ALCHEMY: Capturing High Value from Industrial Fermentation BioProducts

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