Responses to the reviewers’ comments

Ref: Revised Manuscript for Biotechnology for Biofuels (Manuscript ID: BBIO-D-17-00392) entitled “Purification of 2,3-Butanediol
from Fermentation Broth: Process Development and Techno-economic Analysis”

We would like to express our deepest gratitude to the editor and the reviewers for their invaluable comments to improve the manuscript. In
accordance with the reviewers’ comments, the manuscript has been carefully revised to address all the comments and to correct all typographical
errors. We hope these replies and actions to address all the comments and issues by the reviewers. All changes are highlighted with yellow
color in the revised manuscript.

Responses to the comments of Reviewer #1

No. Reviewer’s Comment Replies/ Actions

1 This manuscript proposes a new process of BDO
separation from the fermented mixture of products.
The followings are suggested for the possible
improvement of the study.
The proposed process is designed for the
improvement of a conventional process. However, a
10% of BDO product is wasted in water that is too
much.
We thank the reviewer for the comment. The 10% of BDO product loss might
seem to be not small enough in conventional separation case. But the authors
think the recovery target is still reasonable in the industrial application of alcohol
recovery from fermentation broth because of a significantly diluted solution. The
review article discussing separation technologies for alcohol dehydration (Vane,
2008) also stated the alcohol recovery from fermentation broth could be a wide
range from 80 to 99 %. Since higher recovery requires more separation cost,
there exists optimal target recovery. In this work, the design target of 90wt%
recovery of 2,3-BDO was arbitrarily chosen considering the normal range that
reported earlier (Vane, 2008). The main focus of the work was on to propose a
comprehensive hybrid process development for 2,3-BDO purification from a real

2 A feed of 90% water is extracted with oleyl alcohol in
twice amount of the feed as solvent. Explain why it is
inevitable to waste a large amount of product.
3 Thermodynamic equilibrium equations are not
developed here. Reduce the lengthy derivation of the
equations.
4 In sensitivity analysis, an SQP was applied. Address
how its tuning parameters were selected and what
the constraints were used in the optimization.
fermentation broth, rather than finding the optimal recovery value.
The authors thank the reviewer for the comment. Although its lowest value of KD
H2O and highest selectivity among all solvent candidates considered in Table 2, as
the reviewer pointed out, a large amount of oleyl alcohol seems to be still
required to extract 2,3-BDO with the 90wt% recovery. This limitation is due to its
inherent extraction characteristics for feed mixture. But, it is also clear that oleyl
alcohol is not only to easily extract 2,3-BDO from fermentation broth but also the
most suitable solvent to minimize the solvent loss in the water outlet stream,
compared to other solvent candidates.
The authors thank the reviewer for the suggestion. The equations were not
developed in this work but obtained from Aspen Plus databank. The equations
have a few differences from the published literature since they were tuned by
Aspen Plus process simulator. For this reason, the authors mentioned the
equations of NRTL and UNIQUAC in the manuscript for the reader’s clear
understanding. For example, in NRTL equations, Equations A.2 to A.6 is necessary
to explain each parameter in Equation A.1.
As per suggested by the reviewer, in the revised manuscript the authors have
moved both equations to the additional file (supplementary materials) for
readability.
The authors thank the reviewer for pointing out the optimization method. This
work employed the optimization built-in tool in Aspen Plus which is based on SQP
algorithm.
Commented [W사1]: I try ti explain in this way. But I also
wonder what was your background to choose 90% recovery. can
you tell me it?
Commented [MB2R1]: As I remembered, 90% recovery was
the recovery target that we need to achieve in the 2,3-BDO project.
I got this information from Jimin and Dr. Long, previously. We
discussed it in the meeting.
Then, once I designed the HED, I followed the previous base case
configuration, that has product flow rate: 1691.28 kg/h.
Then, to response this comment, I just found some reference (Vane
et al.) stated the recovery of alcohol could be from 80 to 99%.
Moreover, as I heard from Junaid, the water stream could be
recycled back to the fermentation unit, so that the loss of BDO can
be avoided. But, I am not that sure since I could not find any
reference for this.
In addition, I think 90% also reasonable value since here I just
involved in two projects (VAM process and CO2 removal). The
recovery target from the company were 90-92%. Yet, noting that
10% of the product also not wasted in the water stream.
Commented [W사3]: I guess the tuning parameter is for
optimization algorithm
Commented [MB4R3]: I guess what he meant by tuning
parameters is the manipulated variable (in this work, solvent rate). I
thought he asked the reason how we choose it (solvent rate) as the
tuning parameters.
Moreover, we did not mention it in the original manuscript. Thus, in
the revised manuscript, I added more explanation about
optimization in Page 9-10.
However, do we need to give more explanation about SQP? About
the reason why we select SQP.
If yes, the yellow-highlight was the explanation.
If no, before the submission, please delete the reference that I
highlighted as well. Thank you, Prof.
The built-in optimization function is based on SQP algorithm (Al-Malah, 2016;
Schefflan, 2011). The function is capable of minimizing the objective function by
manipulating the decisive variable. It was shown that the SQP algorithm is
globally and locally superlinearly convergent (Biegler and Cuthrell, 1985; Boggs
and Tolle, 1995).

Moreover, Aspen Plus optimization approach based on SQP algorithm has been
proven to be well-performed for numerous process (Ignat and Kiss, 2013; Kiss
and Ignat, 2012a, b; Kiss and Suszwalak, 2012; More et al., 2010; Sheu and
Mitsos, 2013).

As described in the manuscript, sensitivity analysis result found that the solvent
rate is one of the most important variables in the distillation column design and
operation. Therefore, in this work, the solvent rate was chosen as manipulating
variable to fulfill the output target (product purity). As described in Process
Simulation section, the constraints or design target that have been used in the
optimization were: (1) 2,3-BDO recovery is 90wt%, and (2) 2,3-BDO purity
(99wt%) in the product. The optimal design for each configuration in this work
was obtained by the minimization of total reboiler duty with the optimizing
variables that mentioned earlier.

As per suggested by the reviewer, in the revised manuscript more explanation

about the optimization method has been added and highlighted (Page 9-10).
 Responses to the comments of Reviewer #2
No. Reviewer’s Comment
1 The conventional distillation in this context should be
the extractive distillation column and not the single
complex column proposed as seen in Figure 2 that has
to be compared one to the other. An elaborate
explanation on the comparison between extractive
distillation and hybrid extraction/distillation should be
put forward in terms of energy savings and the total
minimum cost. Comparing the configuration of Figure
2a and 2b will be obvious that the proposed
configuration as in Figure 2b will be superior than that
of Figure 2a.
Replies/ Actions
The authors thank the reviewer for his important comment.
As described in the background section, this work implements a hybrid system
combining solvent extraction with the distillation process. The integrated process
here is called HED. To the authors’ knowledge, there is no literature that
investigates the combination of this technique for recovering 2,3-butanediol from
the fermentation broth. Up to now, only liquid-liquid equilibrium experiments
were carried out to evaluate the solvents performance.
Conventional distillation is the well-known separation of chemical mixtures which
has no azeotrope such as 2,3-BDO and water. However, due to the low
concentration of 2,3-BDO, the high energy required to evaporate all the water
content from the fermentation broth. Therefore, the main aim of this work is to
propose a comprehensive process development for 2,3-BDO purification from a
real fermentation broth, and finally, the energy efficiency and economics of 2,3-
butanediol purification process could be improved by applying the proposed
hybrid design, which evaluated all available solvent comprehensively. Please note
that the energy saving of the proposed configuration is based on the limited-
available LLE data, which have been discussed in Selection of Solvent.
We also agree with the reviewer for the possible potential of extractive distillation
application. Unfortunately, the VLLE data for the corresponding mixture
components and solvent to be applied in the extractive distillation process are not
available. Although it is out of current scope of this work, it would be interesting

2 Complex column such as in Figure 8 shows that heat
integration is used in this case. However, to increase
one degree Celcius from 90 degrees to 91 degrees is
not a common practice for commercial plant.
3 Although the total annual cost for HED is lower than
the conventional column as given in Figure 13,
however the conventional column does not use Oleyl
Alcohol as can be seen in Figure 8. Therefore the
penalty cost for using additional chemicals has not
been taken into account for HED.
to explore the feasibility of an extractive distillation process, and we would like to
save the extractive distillation study with VLLE experiment for a future study.
The authors thank the reviewer for the detailed comment. As mentioned in the
Sensitivity analysis and process optimization section, the objective function is
minimum TAC. Based on the techno-economic analysis, the minimum TAC for
conventional distillation process could be obtained by maximizing the heat
recovery from all distillation outlet as shown in Fig. 8.
Although the optimization results to minimize the TAC gave the configuration in
Fig. 8, we also agree with the reviewer that the heat integration to increase just by
1 degree is not common in practice, and further this heat integration does not give
a notable difference. Nevertheless, we would like to keep the current
configuration in Fig. 8 as a theoretically minimum TAC case and for a comparison
purpose.
The operating cost for using additional chemical (oleyl alcohol) in HED has been
taken into account in total annual cost evaluation. As can be seen in Fig. 13, HED
require operating cost (white stripe) for supplying the make-up solvent. Moreover,
the total annual cost saving of 2,3-BDO process using hybrid extraction distillation
could be further increased if less expensive solvent which has similar or higher
performance with oleyl alcohol is available in the future.
However, as the reviewer pointed out, any process using an additional solvent
inherently accompanies the additional penalty and/or risk. But this penalty cost is
often intangible and hard to quantify as well as marginally affects the TAC. For this
reason, we have not taken into account this penalty cost in this study.
4 Please check Figures 14 and 15 whether they are in
the figure's file.
Responses to the comments of Reviewer #3
No. Reviewer’s Comment
1 Page 4, line 20. The boiling temperature of 2,3-BDO is
177C, not "exceeding 180C".
2 Page 4, line 53, "In general, to obtain high recovery
efficiency, pretreatment of the fermentation output is
necessary to separate the solids and insoluble
content". This sentence does not seem to belong
here. Please double check.
3 Page 7, the section of "thermodynamic model" should
be moved to supplementary information/materials, as
the majority content of this section can be found from
any textbook of thermodynamics on NRTL and
UNIQUAC
The authors thank the reviewer for pointing out the mistakes in writing. What we
meant by Figures 14 and 15 were Figures 12 and 13, respectively. It has been
corrected in the revised manuscript.
Replies/ Actions
The authors thank the reviewer for the comment. As shown in Fig. 5, both
references in VLE data of 2,3-BDO and water showed the boiling temperature of
2,3-BDO exceeds 180oC.
To be clear with the reader, the sentence about boiling temperature of 2,3-BDO
on Page 4 has been modified to “The boiling point of 2,3-BDO at atmospheric
pressure is about 180 °C”.
The authors thank the reviewer for the comment. To avoid the confusion, that
sentence has been removed in the revised manuscript.
The authors thank the reviewer for the recommendation. The equations were
obtained from Aspen Plus databank. The equations itself has a few differences
with the original-published literature. For this reason, the authors mentioned the
equations of NRTL and UNIQUAC in the manuscript. For example, in NRTL
equations, equations A.2 to A.6 is necessary to explain its parameter in Equation
Commented [W사5]: Is it? check the bp from the aspen DB
directly not from T-xy diagram.please ch
Commented [MB6R5]: Yes, Professor.
In Aspen Plus DB, the boiling point of 2,3-BDO is 180.7 C. Rather
than explaining 2,3-BDO boiling point in Aspen Plus DB, the reason
why I response using the VLE data reference is because we have
used those two papers for VLE mixtures.
Moreover, before once I checked other references, I found that
most of 2,3-BDO boiling point stated over 180 C, even up to 184 C.
If it is necessary for the response, please let me know so that I can
added the following references as well.
http://www.sciencedirect.com/science/article/pii/09608524940013
6O
http://www.sciencedirect.com/science/article/pii/S1359511310000
279
https://link.springer.com/article/10.1007/s00253-008-1387-4

4 Fig. 10. The legend (N1=6 and N2=14) needs to be
fixed or corrected.
5 Fig. 11. The total 2,3-BDO yield loss is significant in the
"optimal design of hybrid extraction distillation"
process. How does this product purification recovery
efficiency compared with that is in the conventional
2,3-BDO purification concept used in Figure 12 and
Fig. 13?
A.1.
In the revised manuscript, the authors have moved both equations to the
additional file (supplementary materials) for readability as per suggested by the
reviewer.
The authors thank the reviewer for the comments.
What the authors meant by writing the legend (N1=6 and N2=14) is to describe
the optimal-fixed total number of theoretical stages of subsequent distillation
columns were 6 and 14 for DC-1 and DC-2, respectively.
In the revised manuscript, explanation about the optimal total stages of
subsequent distillation columns has been added for the readers’ clear
understanding (Page 20).
“The optimal total stages for DC-1 and DC-2 were 6 and 14, respectively.”
Actually, as can be evaluated from the mass balance of both proposed
configuration, the flow rate and weight composition of 2,3-BDO product were
same, 1691.28 kg/h with 99wt% of 2,3-BDO. Therefore, the total 2,3-BDO yield
loss for both configurations was same.
It was because of the 2,3-BDO recovery and purity for both proposed
configuration was set at the same level, i.e., 90% 2,3-BDO recovery and 99wt% of
2,3-BDO as the product.
If one found the slight differences in mass balance, it is simply due to the rounding
numbers as shown in the figure (decimal places: 4).
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