Professional Documents
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a r t i c l e i n f o a b s t r a c t
Corresponding author at: Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok 10900, Thailand.
E-mail address: sarote.s@ku.ac.th (S. Sirisansaneeyakul).
http://dx.doi.org/10.1016/j.fbp.2017.07.002
0960-3085/ 2017 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
130 food and bioproducts processing 1 0 5 ( 2 0 1 7 ) 129140
Tochampa et al., 2005; Wannawilai and Sirisansaneeyakul, were washed twice with distilled water and dried at 105 C for
2015). The initial pH of the medium was adjusted to pH 4.0 24 h to measure the dry cell weight (DCW). The supernatant
with 3 M HCl (Sirisansaneeyakul et al., 2013). All media were was used to measure xylose, glucose, xylitol and furfural by
sterilized by autoclaving (121 C, 15 min). HPLC (Knauer, Berlin, Germany). A VertiSepTM SUGAR CMP
HPLC column (7.8 mm 300 mm, 9 m; Vertical Chromatog-
2.2. Preparation of inoculum raphy Co., Ltd., Thailand) was used for measuring xylose,
glucose and xylitol. The mobile phase was deionized water
Two loopfuls of cells from a slant were inoculated into 25 mL at a ow rate of 0.4 mL min1 . The column was held at 80 C.
of the growth medium in a 250-mL Erlenmeyer ask. The cul- A refractive index detector was used. The injection volume
ture was grown aerobically by incubating the ask on a rotary was 20 L. Furfural concentration was measured using an
shaker (250 min1 , 30 C, 24 h). Subsequently, all the culture Eurospher 100-5 C18 column (250 4.6 mm; Knauer, Berlin,
broth was transferred to a 500-mL Erlenmeyer ask containing Germany). The mobile phase was 5% (v/v) acetonitrile at a
225 mL of the growth medium. The inoculum was incubated ow rate of 1.0 mL min1 . The injection volume was 20 L.
for 24 h under the above specied conditions. This culture was The column was kept at 25 C. A UV detector measuring at
used to seed all experiments. a wavelength of 254 nm was used. The fermentation kinetic
parameters were calculated according to Sirisansaneeyakul
2.3. Shake ask cultures et al. (2013).
The volumetric oxygen transfer coefcient (kL a) for a
2.3.1. Effects of furfural on biomass production phase 500 mL nonbafed Erlenmeyer ask was estimated at 30 C
The experiments were carried out in 500-mL Erlenmeyer using the following equations:
asks. Twenty ve milliliters of inoculum was added to 225 mL
of the growth medium. This medium contained 10 g L1 glu- kL a = A ln V + B (1)
cose and 5 g L1 xylose as carbon sources. The initial pH was
4.0. The initial furfural concentration (0, 0.164, 0.462, 0.977, where V (%) was the percentage of the total ask volume lled
1.723 and 2.615 g L1 ) in different asks varied. All asks were with the liquid and the parameters A and B depended on the
held on a rotary shaker (250 min1 ) at 30 C until the glucose shaking speed (n, min1 ) as follows:
and xylose were exhausted. Samples were taken every 4 h to
measure the concentrations of the biomass, furfural, xylose A = 7.0 104 n2 0.4879n 32.622 (2)
and xylitol.
B = 2.1 103 n2 + 1.836n 123.82 (3)
2.3.2. The effect of furfural on xylitol production phase
Our previously reported data on effects of furfural on produc- Eq. (1) is similar to that recommended by Schiefelbein et al.
tion of xylitol (Wannawilai et al., 2017) was used in modeling (2013).
and verication of the fermentation kinetics in the present
work. In brief, the experiments used 500-mL Erlenmeyer asks 2.5. Kinetic model for yeast growth and xylitol
with an initial working volume of 250 mL. Growth medium production
containing glucose (10 g L1 ) and xylose (5 g L1 ) but no furfural
was used in an initial biomass production phase. The initial The effects of furfural were modeled by treating it as a growth
pH was 4.0. All asks were held on a rotary shaker (250 min1 ) inhibitor in view of its known effects (Almeida et al., 2007;
at 30 C until the glucose and xylose were exhausted. At this Liu et al., 2009; Modig et al., 2002; Wannawilai et al., 2017).
point, xylose (30 g L1 ) and (NH4 )2 HPO4 (6 g L1 ) were added. In the absence of the inhibitor, the growth was assumed to
Furfural was added to different asks at various initial con- follow Monod type kinetics in which the specic growth rate
centrations (0, 0.1, 0.2, 0.3, 0.5, 0.75, 1.0 and 2.0 g L1 ). The depended on the concentration of the substrate (S) that could
initial working volume was now 300 mL. The pH was 7.0. The be glucose, xylose or a combination of the two. Thus, the
agitation speed was reduced to 150 min1 and the incuba- biomass concentration (X) at time t depended on the specic
tion temperature was 30 C. All experiments were in duplicate. growth rate with the inhibitor present (I ), as follows:
Samples were taken periodically to measure the concentra-
tions of the biomass, furfural, xylose and xylitol. dX
= I X (4)
dt
2.3.3. Effects of agitation speed on xylitol production
and the specic growth rate I depended on the concentration
Cultures were started as explained above (Section 2.3.2) for
of the substrate (S) and the inhibitor (I), as follows:
the biomass production phase. Subsequently, in the xylitol
production phase (see above), different asks were agitated at max S
I
a
110 min1 and 250 min1 . At the start of the xylitol production I = 1 (5)
KS + S Im
phase, furfural was added to all asks to obtain a concen-
tration of 0.3 g L1 . The initial pH was 7.0 and the incubation In the above equation, max is the maximum specic growth
temperature was 30 C. All experiments were in duplicate. The rate, KS is the saturation constant, Im is the threshold con-
samples were taken periodically for the above specied mea- centration of furfural at which the growth is fully suppressed
surements. (i.e. I becomes zero) and a is the toxic severity coefcient,
a measure of the inhibitory power. For a = 1, an increasing
2.4. Analytical methods concentration of furfural reduces the specic growth rate lin-
early. If a < 1, the specic growth rate declines hyperbolically
The samples of the culture broth were centrifuged (1700 g, as the concentration of furfural increases. For a > 1, the specic
10 min) to separate the cells and the supernatant. The cells growth rate shows a rapid parabolic decline as the concentra-
132 food and bioproducts processing 1 0 5 ( 2 0 1 7 ) 129140
tion of furfural increases. Therefore, a high a-value represents where and are the growth-associated and
a higher toxicity compared to a lower value (Georgieva et al., nongrowth-associated coefcients for product formation,
2007; Lee et al., 2000; Levenspiel, 1980; Wannawilai et al., 2015). respectively.
To determine the type of inhibition that may be occurring In the cell, furfural is converted to less toxic compounds
(e.g. competitive inhibition, uncompetitive inhibition, non- such as furfuryl alcohol (Wang et al., 2017) and furoic acid
competitive inhibition), the various inhibition models (Cer (Horvth et al., 2003; Kundiyana et al., 2009; Liu et al., 2009;
et al., 2009) were tested. These were as follows: Palmqvist et al., 1999). This conversion is assumed to follow
the Michaelis-Menten kinetics; thus,
max S
I = for competitive inhibition (6)
KS 1 + I
+S dI qmax I
KI = I X (13)
dt KF + I
maxI S
1+ K In the above equation qmax
I is the maximum specic consump-
I
I = for uncompetitive inhibition (7) tion rate of furfural and KF is the corresponding saturation
KS
+S
1+ KI constant.
I
The measured furfural concentration was used to calcu-
maxI S late the volumetric (QI ) and specic (qI ) consumption rates of
1+ K furfural as follows:
I
I = for noncompetitive inhibition (8)
KS + S
I2 I1
QI = (14)
In the above equations, KI is an inhibition constant. Depend- t2 t1
ing of the value of KS , furfural may behave as a competitive
QI X2
inhibitor, an uncompetitive inhibitor or a noncompetitive qI = ln (15)
X2 X1 X1
inhibitor (Cer et al., 2009). If is the specic growth rate in the
absence of the inhibitor (i.e. I = 0), then for competitive inhibi- where I1 and I2 are the measured concentrations of furfural at
tion at I = I50 , = 2 I (Cheng and Prusoff, 1973) and, therefore, the beginning (time = t1 ) of fermentation and at the instance
Eq. (6) reduced to the following: (time = t2 ) of total consumption of furfural, respectively; X2 is
the biomass concentration at time t2 ; and X1 is the biomass
I50 concentration at time t1 . Eq. (13) was used to estimate the
KI = S
(9)
KS +1 kinetic parameters qmax and KF .
I
In Eq. (9), I50 is the inhibitor concentration required to reduce 2.6. Estimation of model parameters and statistical
specic growth rate to 50% of the -value in the absence of analyses
the inhibitor. For the case of competitive inhibition, if S = KS ,
KI = 0.5I50 . On the other hand, if S >> KS , the KI << I50 and if The experimental data were used to estimate the kinetic
S << KS , the KI
= I50 . parameters (i.e. max , KS , YX/S , mS , and ) of the
For the case of uncompetitive inhibition at I = I50 , Eq. (7) above referenced models. The parameter values were
modies to the following: selected to produce the best t between the model equa-
tions and the experimental data. Berkeley MadonnaTM
I50
KI = (10) (http://www.berkeleymadonna.com/) software was used for
KS
S +1 the tting. The value of coefcient of determination (R2 )
(Kumar, 2007; Lang et al., 2009) was used to decide on the good-
If S = KS , then KI = 0.5I50 . On the other hand, if S >> KS , then ness of t between the model and the data. R2 was calculated
KI
= I50 and if S << KS , then KI << I50 . Similarly, for noncompet- as follows:
itive inhibition at I = I50 , KI = I50 when S = KS , or S >> KS or S << KS
(Cer et al., 2009; Cheng and Prusoff, 1973).
2
(Ccal Cexp )
The substrate (whether single or mixed) uptaken by the R2 =
2
(16)
2
(Ccal Cexp ) + (Ccal Cexp )
yeast is metabolized for growth, cell maintenance and xylitol
production. Therefore, the substrate consumption rate can be
where Ccal is the value of a variable calculated using the model
modeled as follows:
and Cexp is the corresponding experimentally measured value.
dX
dS 1 1 dP Cexp is the average of all the experimentally measured values
= + mS X+ (11) of the relevant variable.
dt YX/S dt YP/xyl dt
where YX/S is the biomass yield on substrate, mS is the biomass 3. Results and discussion
maintenance coefcient, YP/xyl is the xylitol yield on xylose
( = 0.912 g g1 ; Barbosa et al., 1988), and P is the concentration 3.1. Effect of furfural in biomass and xylitol
of xylitol (the product) at time t. production phases
Xylitol production from xylose is generally described as
a mixed growth-associated product formation. Therefore, Furfural inhibited the yeast growth. It reduced the specic
the production kinetics of xylitol can be modeled using growth rate (Fig. 1A) and the nal biomass concentration
Luedeking-Piret equation, as follows: (Fig. 1B). Furfural extended the duration of the lag phase
(Fig. 1B). The specic growth rate was reduced with increasing
dP furfural concentration in a concentration-dependent manner
= (+)X (12)
dt (Fig. 1A). The length of the lag phase increased nonlin-
food and bioproducts processing 1 0 5 ( 2 0 1 7 ) 129140 133
Fig. 1 Initial furfural concentration (I0 ) in Erlenmeyer asks affects the specic growth rate (I ) (A), the nal biomass
concentration (grey bars) (B) and the length of the lag phase (B). The nal biomass concentration was the corrected
concentration at 28 h in batch culture. The length of the lag phase (lled squares, B) was calculated by tting the batch
growth data using the DMFit software (http://browser.combase.cc/DMFit.aspx).
early with an increasing initial concentration of furfural once 3.2. Kinetic modeling of biomass and xylitol
the concentration exceeded 0.164 g L1 (Fig. 1B). Although production
the lag phase was not inuenced by furfural concentrations
of <0.164 g L1 , both the specic growth rate and the nal In modeling biomass growth, the specic growth rate (I ) was
biomass concentration were negatively impacted relative to taken to depend on the concentration of the inhibitor I (i.e.
controls (no furfural) also by low concentrations (Fig. 1). For furfural). In view of the linear dependence of on I (Fig. 1A),
example, the nal biomass concentration was reduced to the value of a (Eq. (5)) was taken to be unity. A critical thresh-
4.94 g L1 , or 21% relative with control (no furfural) in the old concentration of furfural (Im ) was dened as the value that
presence of furfural at an initial concentration of 0.164 g L1 just completely inhibited growth (I = 0). The measured values
(Fig. 1B). Growth was not completely inhibited by furfural up of , i.e. the specic growth rate in the absence of furfural, and
to 2.615 g L1 (Fig. 1A). Yeasts are known to reduce the adverse I (i.e. the specic growth rate with furfural present at an ini-
impact of furfural by metabolizing it to less toxic products tial concentration I) were used to calculate the ratio I /. This
such as furoic acid or furfuryl alcohol (Horvth et al., 2003; ratio was plotted against the initial concentration of furfural as
Liu et al., 2009; Wang et al., 2017). Therefore, as furfural was shown in Fig. 2. The resulting straight lines were extended to
progressively detoxied the growth rate increased. the x-axis (i.e. to I / = 0) to read the threshold inhibitory con-
In view of the growth inhibitory effects of furfural (Fig. 1), centrations Im for the biomass growth phase and the xylitol
the biomass production phase of the culture should ideally production phase (Fig. 2).
be completely free of furfural. Once a substantial amount of In the biomass growth phase with mixed glucose and
biomass has been generated rapidly in a furfural-free oper- xylose as substrates, the Im -value was 10.183 g L1 (Fig. 2). For
ation, the conversion of xylose to xylitol may be benecially the xylitol production phase with xylose as the sole carbon
carried out in the presence of a certain amount of furfural substrate, the Im value was 7.148 g L1 (Fig. 2). This was con-
in a separate phase of culture as shown later in this work. sistent with values reported for other yeasts. For example,
Although the presence of furfural in the second stage still the critical concentration of furfural for completely inhibit-
inhibited growth (data not shown), this was actually use- ing growth of eight strains of the yeast Candida spp. has been
ful as it allowed more of the xylitol formed from xylose to reported to be 8 g L1 (Lazarova et al., 1990). Similarly, for
be excreted into the culture medium instead being further the yeast Saccharomyces cerevisiae, a furfural concentration of
metabolized to xylulose for production of biomass. An ini- 53 mM ( = 5.1 g L1 ) reduced the specic growth rate to nil as
tial furfural concentration of approximately 0.3 g L1 in the reported by Palmqvist et al. (1999). Based on the Im -values,
xylitol production phase has been previously reported to furfural was more toxic to C. magnoliae TISTR 5663 cells dur-
improve production of xylitol in C. magnoliae (Wannawilai ing the xylitol production phase which operated under oxygen
et al., 2017). limiting conditions with xylose as the sole substrate. For any
134 food and bioproducts processing 1 0 5 ( 2 0 1 7 ) 129140
max S
I
a
Cell growth dX
dt
= KS +S 1 Im X max (h1 ) 0.148 0.0086
KS (g L1 ) 2.319 0.430
Im (g L1 ) 10.183 7.148
a 1 1
Xylose consumption dS
dt
= 1
YX/S
dX
dt
+ mS X+ 1
YP/xyl
dP
dt
mS (g g1 h1 ) 0 0.0014
Xylitol production dP
dt
= ( + ) X (g g1 ) 0.0097 5.956
(g g1 h1 ) 0.0027 0.0018
qmax I
Furfural reduction dI
dt
= KF +I X
I qmax
I
(g g1 h1 ) 0.4465 0.2536
KF (g L1 ) 0.7055 1.169
a
Kinetic parameters were estimated by tting the model equations to the experimental data for the biomass growth and xylitol production
phases with and without furfural in shake ask cultures.
b
In biomass production phase glucose (10 g L1 ) and xylose (5 g L1 ) were used together in 500-mL Erlenmeyer asks with an initial working
volume of 250 mL of growth medium (initial pH = 4.0; temperature = 30 C; agitation speed = 250 min1 ).
c
Xylitol production phase occurred under oxygen-limited conditions with 30 g L1 xylose as the only carbon substrate in 500-mL Erlenmeyer
asks (initial working volume = 300 mL of growth medium; initial pH = 7.0; temperature = 30 C; agitation speed = 150 min1 ).
Table 2 The KI values estimated using the various inhibition models during the biomass production phase in shake
asks.
Inhibition model KI (g L1 ) R2 valuesa
X S P I
Competitive inhibition dX
dt
= maxI S X 0.253 0.8771 0.0408 0.9301 0.0308 0.8146 0.0228 0.9497 0.0275
KS 1+ +S
KI
max S
1+ I
dX KI
Uncompetitive inhibition = X 1.534 0.8770 0.0408 0.9301 0.0309 0.8145 0.0228 0.9494 0.0277
dt
KS
+S
1+ I
KI
max S
1+ I
dX KI
Noncompetitive inhibition dt
= KS +S X 1.788 0.8770 0.0408 0.9301 0.0309 0.8146 0.0228 0.9494 0.0277
X = biomass concentration; S = cosubstrate (glucose and xylose) concentration; P = xylitol concentration; and I = furfural concentration.
a
R2 values are shown as average standard derivation for the model ttings for initial furfural concentrations of 0.164, 0.462, 0.977 and
1.723 g L1 .
Table 3 The KI values estimated using the various inhibition models during the xylitol production phase in shake
asks.
Inhibition model KI (g L1 ) R2 valuesa
X S P I
Competitive inhibition dX
dt
=
max S
X 0.220 0.9874 0.0145 0.9970 0.0022 0.9909 0.0044 0.9272 0.0124
KS 1+ I +S
KI
max S
1+ I
dX KI
Uncompetitive inhibition = X 0.807 0.9899 0.0107 0.9983 0.0011 0.9944 0.0028 0.9265 0.0130
dt
KS
I
+S
1+
KI
max S
1+ I
dX KI
Noncompetitive inhibition dt
= KS +S X 0.820 0.9899 0.0107 0.9983 0.0011 0.9944 0.0028 0.9265 0.0130
three different kinds of inhibition kinetics as summarized in that furfural was much more toxic to yeast during the xylitol
Table 2 for the biomass growth phase and Table 3 for the xyl- production phase compared to the biomass production phase.
itol production phase. Irrespective of the inhibition model, During the biomass production phase when the sub-
the KI value for the biomass production phase (Table 2) was strate concentration (S = 15 g L1 ) was higher than the KS
higher compared to the KI value estimated using the same value ( = 2.319 g L1 ), furfural acted as a competitive inhibitor
model in the xylitol production phase (Table 3). This indicated as the KI -value ( = 0.253 g L1 ) was less than the I50 -value
136 food and bioproducts processing 1 0 5 ( 2 0 1 7 ) 129140
Fig. 4 Comparison of experimental (symbols) and model predicted (lines) fermentation proles for the biomass production
phase with the following initial concentrations of furfural (g L1 ): (A) 0; (B) 0.164; (C) 0.462; (D) 0.977; (E) 1.723; and (F) 2.615.
All fermentations used aerobic conditions at an agitation speed of 250 min1 (X, biomass concentration; S, concentrations of
cosubstrates (glucose and xylose); P, concentration of xylitol; and I, concentration of furfural).
( = 5.092 g L1 ). Similarly, during the early stages of the The initial xylose concentration was 30 g L1 and furfural was
xylitol production phase, furfural likely acted as a compet- added at an initial concentration of 0.3 g L1 . The initial pH
itive inhibitor of growth because the xylose concentration was 7.0 and the incubation temperature was 30 C.
( = 30 g L1 ) was higher than the KS value ( = 0.430 g L1 ) The production kinetic parameters for various agitation
and, therefore, the KI -value ( = 0.220 g L1 ) was less than I50 speeds are summarized in Table 4. A high agitation speed of
( = 3.574 g L1 ). 250 min1 (i.e. an initial kL a 17.22 h1 ; Eq. (1)(3)) resulted
in the highest yield (YP/xyl = 0.536 g g1 ) and productivity
(QP = 0.340 g L1 h1 ) of xylitol as a consequence of a relatively
3.3. Effects of agitation speed on xylitol production in improved supply of oxygen. Although too high a concentra-
shake ask cultures tion of dissolved oxygen is not wanted for xylitol production,
a certain amount of oxygen is necessary. Oxygen transfer
Xylitol production in shake asks was compared at agitation
is improved by increasing the kL a value. At the two lower
speeds of 110 and 250 min1 and with the data obtained earlier
agitation speeds the kL a values were low (kL a 1.24 h1 at
at 150 min1 . Xylitol production was carried out using 500-mL
110 min1 and 2.74 h1 at 150 min1 ).
Erlenmeyer asks with an initial working volume of 300 mL.
food and bioproducts processing 1 0 5 ( 2 0 1 7 ) 129140 137
Fig. 5 Comparison of experimental (symbols) and model predicted (lines) fermentation proles for the xylitol production
phase with the following initial concentrations of furfural (g L1 ): (A) 0; (B) 0.1; (C) 0.2; (D) 0.3; (E) 0.5; (F) 0.75; (G) 1.0; and (H)
2.0. All fermentations used oxygen limited conditions at an agitation speed of 150 min1 (X, biomass concentration; S,
concentration of xylose; P, concentration of xylitol; and I, concentration of furfural).
The effect of dissolved oxygen on the culture could be correlate with the agitation speed (n) of the shaker platform
empirically modeled by modifying Eq. (5) as follows: (Fig. 7), as follows:
max S I
a
I = 1 KO (17)
KS + S Im KO = 8.4 103 n 0.2363 (18)
Fig. 6 Comparison of experimental (symbols) and model predicted (lines) fermentation proles for the xylitol production
phase at the following combinations of agitation speeds (n) and KO values: (A) n = 110 min1 , KO = 0.705; (B) n = 150 min1 ,
KO = 1.0; and (C) n = 250 min1 , KO = 1.871. All experiments were done in 500 mL Erlenmeyer asks with furfural added at an
initial concentration of 0.3 g L1 . The initial working volume was 300 mL (X, Biomass concentration; S, concentration of
xylose; P, concentration of xylitol; and I, concentration of furfural).
3.4. Model validation with a different yeast (Candida guilliermondii FTI 20037; Silva
et al., 1997). The initial working volume was 300 mL. The initial
The model was validated against experimental data not previ- concentration of furfural was 0.3 g L1 . The model equations
ously used in model development. For this, batch experiments (Eqs. (4), (11)(13) and (17)) with the earlier established kinetic
were carried out in 500 mL Erlenmeyer asks, as above, but at parameters shown in Table 1 were used to predict the concen-
an agitation speed of 290 min1 . This agitation speed corre- trations of biomass, xylose, xylitol and furfural during xylitol
sponded to an estimated initial kL a value of 27 h1 that had production. The measured data and the model predictions
been previously reported to be optimal for xylitol production are compared in Fig. 8. The predicted biomass concentrations
food and bioproducts processing 1 0 5 ( 2 0 1 7 ) 129140 139
Volumetric rates (g L1 h1 )
15 0.3
QX 0.003 0.001 0.029 0.003 0.046 0.009
QS 0.301 0.053 0.416 0.010 0.635 0.007 10 0.2
QP 0.132 0.046 0.198 0.007 0.340 0.031
5 0.1
Specic rates
(h1 ) 0.001 0.000 0.007 0.001 0.012 0.002 0 0.0
qS (g g1 h1 ) 0.085 0.002 0.106 0.004 0.164 0.002 0 4 8 12 16 20 24 28 32 36 40
qP (g g1 h1 ) 0.036 0.006 0.050 0.002 0.088 0.010
Yields (g g1 )
YX/S 0.010 0.002 0.069 0.005 0.073 0.014
Fig. 8 The model validation. Comparison of the measured
YP/xyl 0.430 0.076 0.476 0.007 0.536 0.054 data (symbols) with the model predictions (lines) for xylitol
production phase. The agitation speed was 290 min1 . The
a
The experiments were carried out in 500-mL Erlenmeyer asks KO ( = 2.2) used for verication had been calculated with Eq.
using xylose (30 g L1 ) as sole substrate and furfural (0.3 g L1 ). The
(18) (Fig. 7). The data shown are average values of two
initial working volume was 300 mL. The temperature was 30 C
experiments done in parallel in 500 mL Erlenmeyer asks
and the initial pH was 7.0.
b
The estimated initial kL a values (see Eqs. (1)(3)) were as follows: with an initial furfural concentration of 0.3 g L1 and an
1.24 h1 at agitation speed of 110 min1 ; 2.74 h1 at agitation speed initial working volume of 300 mL (X, biomass concentration
of 150 min1 ; and 17.22 h1 at agitation speed of 250 min1 . (open circles); S, concentration of xylose (open triangles
up); P, concentration of xylitol (open squares); and I,
concentration of furfural (lled triangles down)).
4. Conclusion
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