Bioprocess and Biosystems Engineering (2018) 41:1697–1706

https://doi.org/10.1007/s00449-018-1993-1

RESEARCH PAPER

Kinetic analysis of sodium gluconate production by Aspergillus niger

with different inlet oxygen concentrations
Xiwei Tian1 · Yuting Shen1 · Yingping Zhuang1 · Wei Zhao2 · Haifeng Hang1 · Ju Chu1

Received: 17 May 2018 / Accepted: 25 July 2018 / Published online: 30 July 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Abstract
To further understand fermentation kinetics of sodium gluconate (SG) production by Aspergillus niger with different inlet
oxygen concentrations, logistic model for cell growth and two-step models for SG production and glucose consumption were
established. The results demonstrated that the maximum specific growth rate (µm) presented exponential relationship with
inlet oxygen concentration and the maximum biomass (Xm) exhibited linear increase. In terms of SG production, two-step
model with Luedeking–Piret equation during growth phase and oxygen-dependent equation during stationary phase could
well fit the experimental data. Notably, high inlet oxygen concentration exponentially improved SG yield (YP/S), whereas
biomass yield to glucose (YX/S) and cell maintenance coefficient (m) were almost independent on inlet oxygen concentration,
indicating that high oxygen supply enhancing SG synthesis not only functioning as a substrate directly, but also regulating
glucose metabolism towards SG formation. Finally, the applicability and predictability of the proposed models were further
validated by additional experiments.

Keywords  Aspergillus niger · Sodium gluconate · Oxygen · Kinetics

Introduction Great efforts have been made either on high-yielding

Sodium gluconate (SG), which is produced commercially
by Aspergillus niger, is extensively used in the food, phar-
maceutical, construction, and detergent industries [1, 2].
The SG biosynthesis can be considered as a simple dehy-
drogenation process catalyzed by glucose oxidase (GOD)
and catalase (CAT). The former enzyme converts glucose to
glucono-δ-lactone along with the hydrogen peroxide forma-
tion, which will be subsequently decomposed to water and
oxygen by the latter enzyme. Simultaneously, the glucono-δ-
lactone is hydrolyzed to gluconic acid either spontaneously
or by lactonase (LAC) [3].
* Haifeng Hang
hanghaifeng@ecust.edu.cn
* Ju Chu
juchu@ecust.edu.cn
1
State Key Laboratory of Bioreactor Engineering, East China
University of Science and Technology, 130 Meilong Road,
P.O. box 329, Shanghai 200237, People’s Republic of China
2
Shan Dong Fuyang Biological Technology Co., ltd, Dezhou,
China
strain screening [4, 5] or on fermentation optimization [6–9].
Simultaneously, with the further understanding of the SG
biosynthesis process by A. niger [9–13], it could be con-
cluded that: (1) the fermentation was generally ended by the
exhaustion of glucose exhaustion, rather than the decrease of
cell or enzyme activity in batch and fed-batch fermentation
modes; (2) the mycelia of A. niger was regarded as a natural
carrier for GOD enzyme and the GOD activity was not the
limiting factor for SG synthesis in batch fermentation; and
(3) the SG fermentation was an extremely oxygen-consum-
ing bioprocess and in comparison the oxygen transfer rate
(OTR) in the bioreactor was always the limiting factor for
SG production. Thus, it was reasonable to speculate that
the strategies that could enhance the OTR would be ben-
eficial for the SG production. In our previous studies, dif-
ferent enriched oxygen concentrations in the air have been
utilized for efficient SG fermentation [14]. Moreover, on-line
physiological parameters, oxygen uptake rate (OUR), carbon
dioxide evolution rate (CER), and respiratory quotient (RQ)
could be applied to real-time monitor the key parameters of
cell growth and SG production [15].
However, how to further apply these physiological param-
eters to formulate dynamic models to study and understand

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the dynamic behavior of SG production was still a challenge.
Dynamic modeling and simulation of the bioprocesses could
provide insights into fermentation process design, regula-
tion, and control to realize the fermentation performance
maximization [16]. Many reports have developed mathemat-
ical models to characterize cell growth, substrate consump-
tion, and product formation by A. niger [17–19]. Monod
and logistic models were adopted as the most applicable
models for cell growth; however, the former was constrained
in SG fermentation process due to the presence of oxygen
limitation, apart from the limitation of nitrogen or phos-
phate sources during the cell growth phase. In contrast,
logistic equation could well reflect the relationship between
the cell growth rate and the biomass. On the other hand, it
was pointed out that the SG biosynthesis was partly asso-
ciated with cell growth, thus Luedeking–Piret (LP) model
was applied to describe this bioprocess [19]. It was notable
that the biomass or GOD activity might be a limiting factor
during the cell growth phase and the SG production would
exhibit a positive relationship with the cell growth. While
the cells entered into the stationary phase, oxygen supply
seemed to be a limiting factor in presence of excess GOD
activity in the broth. Fortunately, as aforementioned, OUR as
a process physiological parameter could be directly adopted
to on-line characterize cellular oxygen metabolism [14, 20,
21] and then further to represent the oxygen supply level.
In this study, on the basis of our previous works on SG
fermentations with oxygen-enriched conditions [14] and the
classic logistic and LP models, modified mathematic mod-
els introducing on-line physiological parameter (OUR) and
environmental operating parameter (inlet oxygen concentra-
tion) for describing cell growth, SG production and glucose
consumption in stages were explored for the first time.
Materials and methods
Microorganism and medium
An industrial strain of A. niger CICC40350 which was pro-
vided by Fuyang Biological Technology Co. Ltd. (Shan-
dong, China) was used in this study.
Three media were used in this work. Activation medium
(g/L): glucose 60, K­ H2PO4 0.13, Urea 0.2, ­MgSO4 0.02,
corn steep liquor (Fuyang Biology Co., Ltd, China) 1,
­CaCO3 5, and agar 20.0. Seed culture medium (g/L): glu-
cose 250, K­ H2PO4 0.6, (­ NH4)2HPO4 0.25, M­ gSO4 0.19,
corn steep liquor 8, and polyether defoamer (Sixin Sci-
entific-Technological Application Research Institute Co.,
Ltd, Nanjing, China) 0.30 mL/L. Fermentation medium:
glucose 320, K­ H2PO4 0.17, (­ NH4)2HPO4 0.25, M
­ gSO4 0.2,
corn steep liquor 2, and polyether defoamer 0.3 mL/L. All
13
Bioprocess and Biosystems Engineering (2018) 41:1697–1706
media were adjusted to a pH range between 6.5 and 7.0 by
4 M NaOH solution.
Culture condition
The strain was activated in a 250 mL eggplant bottle with
a slant of 50 mL activation medium. Then, the eggplant
bottle was incubated at 35 °C for 60 h and the spores were
harvested by 50 mL sterilized water for inoculation. In
seed culture, the strain was cultured in a 250 mL shake
flask with 50 mL working volume at 37 °C, 220 rpm for
17 h.
A 5  L stirred bioreactor (Guoqiang Bio-engineering
Equipment Co. Ltd., Shanghai, China) with 3 L working
volume in batch fermentation was carried out in this study.
The fermentation temperature, overpressure, and aeration
were set at 38 °C, 0.05 MPa, and 1.3 vvm. Inlet oxygen
concentrations were controlled at 21, 25, 27, 29, and 32%,
respectively, by regulating the appropriate proportion of
air and pure oxygen. A two-stage agitation strategy (0–6 h,
500 rpm and 6 h-end, 800 rpm) was employed during the
whole process and the broth pH was controlled at 5.5 by
7.5 M NaOH solution. The fermentation was ended when
the residual glucose concentration was less than 3 g/L. All
experiments were performed in triplicate. All data used for
the model calculation in the tables and figures were the aver-
age values of three independent experiments.
Analytic methods
Assay of cell growth
Cell biomass was expressed as dry cell weight (DCW).
30 mL broth was filtered through a 0.45 µm membrane,
and the mycelia were washed five times by deionized water.
After drying at 105 °C for 48 h, the filter paper was weighted
and the DCW equaled to the net weight difference of the
filter paper.
Glucose and SG determination
Glucose concentration was determined by an assay kit
(Shanghai Kexin Biotech Co., Ltd, China) after appropriate
dilution. SG was quantitatively measured by high-perfor-
mance liquid chromatography (SPD-20A, Shimadzu, Japan)
at 210 nm with a C-18 column (4.6 × 250 mm, no. 336–1101,
Sepax Technologies, Inc, USA). The mobile phase was
prepared with isovolumetric methanol solution (3 M) and
phosphate solution (0.25 M). The flow rate and the working
temperature were set at 1 mL/min and 28 °C, respectively.
Bioprocess and Biosystems Engineering (2018) 41:1697–1706 1699

OUR determination 𝛼X0 Xm e𝜇m t 𝛽Xm

(
X0 e𝜇m t + Xm − X0
)
P= 𝜇 t
+ × ln
Xm − X0 + X0 e m 𝜇m Xm
Online physiological parameter, OUR, was calculated in
+ A (0 ≤ t ≤ 8) (6)
real-time as described by Wang et al. [21] through the fol-
lowing equation: dP
= 𝛾 + 𝛿 × OTR (8 < t < te ) (7)
[ ] dt
Fin Cinertin × CO2 out 273
OUR = CO2 in − ) ×
(8)
(
V 1 − CO out + CCO out 273 + tin P = (𝛾 + 𝛿 × OTR) × (t − 8) + P8 (8 < t < te ),
2 2

1 (1) where P (g/L) P8, and te (h) were SG concentration, SG

× Pin × × 10−5 ,
1+h concentration at 8 h, and fermentation ending time. OTR
was the oxygen transfer rate during stationary phase under
where Fin was the inlet flow rate; CO2 in , CCO2 in , and Cinert in
different oxygen-rich air conditions. α, β, γ, δ, and A were
were the mass fraction of oxygen, carbon dioxide, and nitro-
constants.
gen in the inlet gas; CO2 out and CCO2 out were the mass fraction
Glucose was utilized mainly for three parts, including bio-
of oxygen and carbon dioxide in the exhaust gas; tin and Pin
mass component synthesis, SG product, and energy supply
were the temperature and pressure of the inlet gas, respec-
for cell maintenance and metabolism. Therefore, glucose con-
tively; V was the working volume; and h was the humidity
sumption could be formulated as follows:
of the inlet gas.
dS dX dP
− = YX∕S × + YP∕S × +m×X (9)
Batch model formulation dt dt dt

In carrying out an overall balance for the biomass, the fol- X0 Xm e𝜇m t X X m
lowing equation was given as: S=S0 − 𝜇 t
+ 0 − m
YX∕S (Xm − X0 + X0 e m ) YX∕S 𝜇m
dX (
Xm − X0 + X0 e 𝜇 t )
(2)
m
= 𝜇 × X. × ln
dt Xm
(10)
For the specific growth rate, dynamic model of logistic 𝛼X0 Xm e𝜇m t
[
1 𝛽Xm m
equation was adopted as follows. − +
YP∕S Xm − X0 + X0 e𝜇m t 𝜇m
Xm − X0 + X0 e𝜇m t
[ ] ( ) ]
dX X
= 𝜇m × X × 1 − (3) × ln + A − P0 (0 ⩽ t ⩽ 8)
dt Xm Xm

X0 Xm e𝜇m t X0 Xm e𝜇m t X
X= , (4) S = S0 − + 0
Xm − X0 + X0 e𝜇m t YX∕S (Xm − X0 + X0 e𝜇m t ) YX∕S
Xm − X0 + X0 e𝜇m t
( )
X m
where X (g/L), t (h), µ (1/h), µm (1/h), and Xm (g/L) were − m × ln (11)
𝜇m Xm
cell biomass, fermentation time, specific growth rate, maxi-
mum specific growth rate, and maximum cell biomass, 1
− [𝛾t + 𝛿t × OTR + P8 − P0 ] (8 < t < te ),
respectively. YP∕S
In regards to SG production, during the cell growth phase, where S (g/L), S0, YX/S (g/g), YP/S (g/g), m (g/g/h), and P0
GOD enzyme was the key factor for SG production and then represented glucose concentration, initial glucose concen-
LP model could well describe this dynamic process. Dur- tration, yield of biomass to glucose, yield of SG to glucose,
ing the stationary phase, oxygen supply became the limit- cell maintenance coefficient, and initial SG concentration,
ing element and the SG production seemed OTR-dependent, respectively.
whereas biomass-independent. Thus, two-step mathematic
model was applied according to cell physiological state as Model parameterization and validation
presented in the following equations:
On the basis of experimental data, software Origin 9.0 (Origin-
dP dX Lab, USA) was used to optimize the parameters in the models
=𝛼× +𝛽×X (0 ≤ t ≤ 8) (5)
dt dt for cell growth, SG production and glucose consumption. Sub-
sequently, an additional experiment was conducted to validate
the fitness of the models.

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1700
Fig. 1  Time courses of cell growth in SG fermentation by A. niger
with inlet oxygen concentrations of 21% (a), 25% (b), 27% (c), 29%
(d), and 32% (e). Scatter: experimental data, line: logistic model
curves
Fig. 2  Effects of inlet oxygen concentration on maximum biomass (Xm) (a), maximum specific growth rate (µm) (b), and SG yield to glucose
(YP/S) (c) in SG production by A. niger. Scatter: experimental data, line: fitting model
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Bioprocess and Biosystems Engineering (2018) 41:1697–1706
Results and discussion
Parameters estimation and model evaluation
Model for cell growth
Although macroscopic comparisons have been investi-
gated in our previous works [14], which demonstrated that
the increase of oxygen concentration in the inlet air would
significantly affect cell growth and metabolism, this study
focused on characterizing the SG batch fermentation with
mathematical models. According to the data of cell growth
as described in our previous works [14], the logistic fitting
curves and corresponding parameters for cell growth with
oxygen concentration of 21, 25, 27, 29, and 32% are shown
in Fig. 1, respectively. The inoculum was prepared under
same operating conditions, and the initial biomass (X0) was
controlled at approximate 0.59 g/L with all inlet oxygen
concentrations. Notably, the maximum biomass (Xm), the
maximum specific growth rate (µm), and SG yield (YP/S)
were greatly dependent on the inlet oxygen concentration
(Fig. 2A, B), which increased from 1.65 g/L, 0.436 1/h, and
Bioprocess and Biosystems Engineering (2018) 41:1697–1706 1701
1.037 g/g to 2.62 g/L, 0.58 1/h, and 1.094 g/g, respectively,
when inlet oxygen concentration rose from 21 to 32%. These
results indicated that for the cell growth, oxygen was con-
sidered to be a limiting factor, besides the nutrients as the
­NH4–N concentration in the broth has already decreased to
zero after about 4 h culture, and high oxygen supply would
be beneficial for the SG production, probably due to the
enhancement of cell respiration efficiency as described by
Diano et al. [22] and by Lu et al. [15]. All the determination
coefficients (R2) were more than 0.97 with the inlet oxygen
concentrations of 21, 25, 27, 29, and 32% conditions, mean-
ing that the logistic model, which has been adopted in other
bacteria and fungus [23–25], could well formulate the cell
growth process in SG fermentation by A. niger.
Moreover, with the consideration of oxygen effect on cell
growth, it was assumed that above the oxygen-independent
µm (µm0), the change of the µm was considered to be linearly
dependent on the change of the oxygen supply. Thus, the
logistic equation was introduced to characterize the rela-
tionship between the µm and the inlet oxygen concentration
as below:
d𝜇m
dCO2
= 𝜌 × (𝜇m − 𝜇m0 ) (12)
( )
𝜇m = e
𝜌×CO2 +B
+ 𝜇m0 , (13)
where µm, CO2, and µm0 represented the maximum specific
growth rate, inlet oxygen concentration, and the maximum
specific growth rate with oxygen non-limited condition,
respectively. ρ and B were constants.
As illustrated in Fig.  2b, the R2 reached 0.994, dem-
onstrating that this model could be applicable to provide
estimation of maximum specific growth rate with different
inlet oxygen concentrations. Previous studies used polyno-
mial model with no biological interpretation to describe
the effects of environmental factors; however, these models
always were limited by their usefulness for further prediction
[26, 27]. In contrast, the parameters of Logistic models for
µm and X in this study were considered to be biologically
interpretable, and could help to better understand the cell
growth process of A. niger.
Model for SG production
The SG batch fermentation by A. niger could be divided into
two phases, as the growth phase (0–8 h) and the stationary
phase (8 h-end) in light of the cell physiological state [14].
During the growth phase, the SG production was regarded
to be partly related with the cell growth. While during the
stationary phase, catalytic carrier (biomass or enzymes) was
sufficient for SG synthesis, and correspondingly, oxygen
supply was the main limiting step. Basing on these anal-
yses, a two-step model with LP model during the growth
phase and a linear OUR-dependent model during the sta-
tionary phase was developed in this study as formulated in
Eqs. (5)–(8).
Through fitting the SG data in the growth phase with dif-
ferent inlet oxygen concentrations, α and β values, which
represented the growth related coefficient and the non-
growth related coefficient, respectively, could be obtained by
5.1 and 10.5 (Fig. 3a; Table 1), indicating that SG produc-
tion majorly presented a non-growth associated characteris-
tic, which was not agreed with the results by Liu et al. [19]
that SG production was a highly cell growth-dependent pro-
cess. This could be contributed to the different strain proper-
ties and culture conditions, such as agitation and aeration.
On the other hand, when the cells entered into stationary
phase, it was observed that the SG concentration was lin-
early increased with fermentation time (Fig. 3b), meanwhile,
the SG productivity exhibited a linear relationship with the
average OUR level at the stationary phase by γ and δ values
of 6.13 and 0.19, respectively (Fig. 3d). This result further
verified that oxygen supply was the only limiting factor for
SG production during stationary phase. It was inferred that
the process strategies of increasing inlet oxygen concentra-
tion could significantly enhance SG production. Previous
study mainly concentrated on the SG production model by
one-step equation without considering different limiting con-
ditions occurred in the different physiological stages [19].
The biomass (or key enzymes) and oxygen were two sub-
stantial elements to guarantee SG efficient production with
sufficient glucose in the broth. And it was believed that the
biomass and oxygen supply were SG production constraints
during the growth and stationary phases, respectively. There-
fore, a two-step model in this work would better describe
the SG production process. In addition, on-line physiologi-
cal parameter, OUR, could be directly introduced into SG
production model during stationary phase and more impor-
tant, this model could be extended to other process strategies
of increasing oxygen supply for the SG fermentation by A.
niger.
Model for glucose consumption
As formulated by Eqs. (9)–(11), the glucose as a substrate
was consumed for three parts, including the carbon back-
bone synthesis for cell growth, the SG production and the
energy supply for cell maintenance. Similar to SG produc-
tion, a two-step model was adopted for glucose consump-
tion and the model could well fit the experimental data with
different inlet oxygen concentrations (Fig. 4A). Notably,
other than the yield of the SG to the glucose (YP/S), which
performed greatly positive relationship with oxygen concen-
tration (Fig. 2c), both the yield of the biomass to the glucose
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1702 Bioprocess and Biosystems Engineering (2018) 41:1697–1706

Fig. 3  Time courses of SG production with different inlet oxygen SG productivity (d) at stationary phase. Scatter: experimental data,
concentrations during growth phase (a) and stationary phase (b) by A. line: predicted values
niger. Effects of inlet oxygen concentration on average OUR (c) and

Table 1  Estimation of model Parameter Estimated value

parameters on SG fermentation
by A. niger with different inlet Growth related coefficient (α) 5.1
oxygen concentrations
Non-growth related coefficient (β) 10.5
Yield of biomass to glucose (YX/S, g/g) 0.083
Cell maintenance coefficient (m, g/g/h) 0.884
Oxygen-independent maximum specific growth rate (µm0, 1/h) 0.431
Oxygen-independent yield of SG to glucose (YP/S0, g/g) 1.023
Initial glucose concentration (S0, g/L) 325
Initial SG concentration (P0, g/L) 22

(YX/S, 0.083 g/g) and the cell maintenance coefficient (m, predict well on YP/S, and the predicted data were basically
0.884 g/g/h) were nearly independent on the inlet oxygen consistent with the experimental results
concentration (Fig. 4b; Table 1). As regards the ­YP/S, higher
inlet oxygen concentration leaded to higher YP/S, indicating dYP∕S
that both the functions of oxygen as a substrate and glu-
= 𝜀 × (YP∕S − YP∕S0 ) (14)
dCO2
cose metabolism towards SG formation contributed to SG
production improvement. Similar to µm, above the SG yield
limiting by other factors rather than oxygen, the SG yield YP∕S = e(𝜀×CO2 +C) + YP∕S0 , (15)
change was dependent on the change of inlet oxygen con-
centration, and logistic equations of (14) and (15) for SG where YP/S0 meant the oxygen-independent SG yield. ε and
yield were expressed. As shown in Fig. 2c, the model could C were constants.

13
Bioprocess and Biosystems Engineering (2018) 41:1697–1706 1703

Fig. 4  Time courses of glucose consumption in SG fermentation by predicted values. Effects of inlet oxygen concentration on the yield
A. niger with different inlet oxygen concentrations of 21% (a), 25% of biomass to glucose (YX/S) and cell maintenance coefficient (m) (F)
(b), 27% (c), 29% (d), and 32% (e). Scatter: experimental data, line:

Oxygen was mainly consumed for SG synthesis (OUR1)
and cell maintenance (OUR2) during the stationary phase,
as cell growth has ceased at that time. Through a simple
biochemical reaction, it could be known that 0.5 mol oxygen
would be consumed to synthesize 1 mol SG. Thus, during
the stationary phase, OUR1 and the glucose consumption
rate using for cell maintenance could be calculated from
the SG productivity as well as maintenance coefficient (m)
and cell biomass (X), respectively (Fig. 5a, b). Subsequently,
OUR2 was further obtained by subtracting OUR1 from the
total OUR (Fig. 5a). Assuming that the glucose was con-
sumed by complete oxidative phosphorylation process, as
1 mol glucose catabolism accompanied with 6 mol oxygen
consumption, thus the minimum glucose requirement for
cell maintenance without other metabolic bypasses could
be acquired through OUR2 values as shown in Fig.  5b.
However, in real fermentation process, it usually existed
non-ideal situation with the byproduct formation, and the
actual glucose consumption amount was much bigger than
the minimum value (Fig. 5b). High inlet oxygen concentra-
tion could improve the glucose consumption efficiency by
the respiratory metabolism from 30.2 to 37.9% (Fig. 5b),
which was in great agreement with our previous results by
metabolic flux analysis [14], and this also accounted for the
SG yield improvement to some extent.
Model validation
The simulated data of cell growth, SG production, and glu-
cose consumption with different inlet oxygen concentra-
tions were in good agreement with the experimental data,
implying that the models proposed in this study adequately
represented the real process. In the following experiments,
additional three independent SG batch fermentations were
conducted with 26% inlet oxygen concentration to validate
the availability and predictability of the models. Figure 6

Fig. 5  Effects of inlet oxygen concentration on OUR (total, OUR1 for SG production and OUR2 for cell maintenance) (a) and glucose consump-
tion (glucose for cell maintenance and calculated glucose by OUR2 with respiratory metabolism) (b)

13

1704 Bioprocess and Biosystems Engineering (2018) 41:1697–1706

Fig. 6  Model validation through the comparisons of experimental data and model predicted values for biomass concentration (a), SG production
(b), and glucose consumption (c) with inlet oxygen concentration of 26% in SG fermentation by A. niger 

illustrates that the kinetic models could finely predict all
the experimental data of cell biomass, SG concentration,
and glucose concentration during the whole fermentation
process.
As a complex bioprocess of fermentation, it was often
difficult to obtain a complete profile to reveal what actu-
ally happened during the whole process and predict the cell
growth and metabolism kinetics under a certain condition.
Although an enormous amount of researches have been car-
ried out on the mathematical modeling of the microbial pro-
cesses [28–30], the applicability of the biological concepts
into the models remained limited. For the SG production
by A. niger, it has been widely reported that oxygen played
an important role on cell growth and metabolism [2, 9,
12], and oxygen supply increase by enhancing inlet oxygen
concentration did boost the cell growth, SG productivity
and SG yield. However, to the best of our knowledge, few
kinetic studies on SG fermentation have taken the oxygen
supply into consideration. Compared to the traditional one-
step LP or LP-like model for SG production and glucose
consumption, two-step models proposed in this work not
only took the cellular oxygen metabolism into considera-
tion, but also introduced physiological parameter (OUR) as
a key model parameter to characterize the process SG and
glucose evolutions, which has not been ever reported in the
literatures. Moreover, the models in the present work could
perfectly predict the SG fermentation process under other
inlet oxygen concentration (ranging from 21 to 32%) condi-
tions. In the follow-up works, different oxygen supply strate-
gies with combined the regulation of agitation, airflow and

13
Bioprocess and Biosystems Engineering (2018) 41:1697–1706 1705
inlet oxygen concentration would be extended. And then,
on the basis of the models in this work, broader process
control modes and technologies could be further understood,
which was believed to be helpful for guiding industrial SG
fermentation by A. niger.
Conclusion
Logistic model for cell growth and advanced two-step mod-
els for SG production and glucose consumption were estab-
lished with different inlet oxygen concentrations in SG pro-
duction by A. niger. According to different cell physiological
and metabolic states, physiological parameter (OUR) was
directly integrated into the two-step model. Moreover, all the
biologically interpretable parameters in this model could be
further formulated by two essential environment variables
(fermentation time and inlet oxygen concentration). Finally,
it was validated that the models could well predict the cell
growth and metabolism kinetics with inlet oxygen concen-
tration between 21–32%.
Acknowledgements This work was financially supported by
the National Science Foundation for Young Scientists of China
(31700038), the National Key Research and Development Program
(2017YFB0309302), and the Fundamental Research Funds for the
Central Universities (WF1814032, 22221818014).
Compliance with ethical standards  novel approach for real-time monitoring of sodium gluconate
Conflict of interest  The authors declared that they have no competing
interests.
Ethical statement  This article does not contain any studies with human
participants or animals performed by any of the authors.
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