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A kinetic model for flavonoid production in tea cell culture

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Abstract

As one of the strategies for efficient production of a metabolite from cell cultures, a kinetic model is very useful tool to predict productivity under various culture conditions. In this study, we propose a kinetic model for flavonoid production in tea cell culture based on the cell life cycle and expression of PAL, the gene encoding phenylalanine ammonia-lyase (PAL)—the key enzyme in flavonoid biosynthesis. The flavonoid production rate was considered to be related to the amount of active PAL. Synthesis of PAL was modelled based on a general gene expression/translation mechanism, including the transcription of DNA encoding PAL into mRNA and the translation of PAL mRNA into the PAL protein. The transcription of DNA was assumed to be promoted at high light intensity and suppressed by a feedback regulatory mechanism at high flavonoid concentrations. In the model, mRNA and PAL were considered to self-decompose and to be lost by cell rupture. The model constants were estimated by fitting the experimental results obtained from tea cell cultures under various light intensities. The model accurately described the kinetic behaviors of dry and fresh cell concentrations, glucose concentration, cell viability, PAL specific activity, and flavonoid content under a wide range of light intensities. The model simulated flavonoid productivity per medium under various culture conditions. Therefore, this model will be useful to predict optimum culture conditions for maximum flavonoid productivity in cultured tea cells.

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Abbreviations

DCW:

Dry cell weight

FCW:

Fresh cell weight

PAL:

Phenylalanine ammonia-lyase

C Ed :

Specific activity of PAL per cell (kat/gDCW)

C Md :

mRNA content per cell (/gDCW)

C Pd :

Flavonoid content per cell (mg/gDCW)

C Pd,max :

Maximum flavonoid content per cell (mg/gDCW)

E :

Specific activity of PAL per medium (kat/dm3)

I :

Light intensity (lux)

k Ed :

Rate constant of PAL self-decomposition (/day)

k Eg :

Rate constant of PAL translation (kat/day)

k i :

Rate constant of cell rupture (/day)

K l :

Light inhibition constant of vacuole formation (lux)

k Md :

Rate constant of mRNA self-decomposition (/day)

k Mg :

Rate constant of transcription (/gDCW/day)

k Pg :

Rate constant of flavonoid production (mg/kat/day)

k s :

Rate constant of cell lysis (/day)

K vb :

Light inhibition constant of non-vacuole formation (lux)

k w :

Water content of non-vacuole (–)

L m :

Light saturation constant of transcription (lux)

M :

mRNA amount per medium (/dm3)

P :

Flavonoid amount per medium (mg/dm3)

S :

Glucose concentration (g/dm3)

t :

Culture period (day)

X d :

Dry cell concentration (gDCW/dm3)

X f :

Fresh cell concentration (gFCW/dm3)

X l :

Vacuole concentration (g/dm3)

X nb :

Non-viable non-vacuole concentration (g/dm3)

X vb :

Viable non-vacuole concentration (g/dm3)

V :

Cell viability (–)

Y :

Yield of non-vacuole on substrate (–)

Z :

Vacuole formation rate constant (/day)

α :

Light promotion coefficient of transcription (–)

μ :

Specific growth rate constant (dm3/g/day)

χ :

Vacuole content (–)

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Authors and Affiliations

  1. Department of Chemical Engineering, Tohoku University, Sendai, Japan

    Naomi Shibasaki-Kitakawa, Yasuhiro Iizuka & Toshikuni Yonemoto

  2. Interdisciplinary Research Center for Catalytic Chemistry, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan

    Atsushi Takahashi

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  1. Naomi Shibasaki-Kitakawa
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  2. Yasuhiro Iizuka
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  3. Atsushi Takahashi
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  4. Toshikuni Yonemoto
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Correspondence to Naomi Shibasaki-Kitakawa.

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Shibasaki-Kitakawa, N., Iizuka, Y., Takahashi, A. et al. A kinetic model for flavonoid production in tea cell culture. Bioprocess Biosyst Eng 40, 211–219 (2017). https://doi.org/10.1007/s00449-016-1688-4

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  • DOI: https://doi.org/10.1007/s00449-016-1688-4

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