(426e) Process Design of Chemo-Enzymatic Synthetic Cascades

Chemo-enzymatic
synthesis is a new method to achieve selective catalysis, with potential
application to many classes of reactions where conventional approaches are
difficult. A combination of enzymatic as well as heterogeneous and homogeneous
catalysis will direct the reaction toward the desired products. Therefore, this
new approach has a potential application in many biosynthetic processes as well
as pharmaceutical processes. However, in many chemo-enzymatic synthesis
processes, even a small reaction pathway,
there are many alternative technologies. Some can be integrated together, some
give the required yield and selectivity, some are difficult to implement and
others are untested at scale (Boisen et al., 2008). Thus, this makes it very
difficult to justify effort and resources on process design in the early stage
of process development when the information is limited (Shaeri et al., 2006).
Therefore, there is a need for a methodology capable of fast evaluation of different
processes with limited information in order to reduce the number of potential
process flowsheets. The purpose is to set targets for further improvement of
the best process options for further improvement, and finally identify the
optimal set of products and the best route for producing them (Sammons et al.,
2007; Shaeri et al., 2006).

Here
we propose a methodology of using a computer aided model framework for process
design of chemo-enzymatic synthetic cascades. The first step in the methodology
is to list all the possible process flowsheets, which involve all the
alternative technologies and routes. After that, a fast process screening is
performed. To do a fast process screening, process model (e.g., Software
PRO/II) is used to obtain the mass and energy balance for different flowsheets.
Based on the simulation results, the raw material and energy cost for producing
1 kg final product of different process options is estimated and compared to
eliminate unattractive flowsheets and to select the most promising process
flowsheets for further analysis. For the selected process flowsheets,
sensitivity analysis together with the cost analysis is performed to identify
the bottlenecks of the flowsheets and ways for improving the process.
Furthermore, other criteria like environmental factors, technical feasibility,
safety, scale-up possibilities are included to optimize the process and
identify the most likely process. Finally, targets for
catalyst and process improvements are set.

As
an example, a case study of process design of chemo-enzymatic synthetic cascades from glucose is used
to illustrate how to apply the proposed methodology in chemo-enzymatic
synthetic process design. The study aims to
produce  2,5-furandicarboxylic acid (FDA) from glucose via the intermediate
5-hydroxymethyl furfural (HMF) and employs a combination of chemical and
enzymatic catalysis as well as novel reactor design. FDA is a new building
block for the polymer industry with applications and properties similar to
terephthalic acid, which is derived from fossil resources and is the main
building block in polyethylene terephthalate based resins and fibers.

HMF
is an important intermediate product, which can be converted to several
valuable products, including oxidation to FDA. In aqueous media, HMF may also
be hydrolyzed to levulinic acid and formic acid. Both FDA and levulinic acid
are listed in the top 12 value-added chemicals for building blocks for industry
(Werpy and Petersen, 2004). HMF can be obtained by dehydration of hexoses. The
dehydration of fructose to HMF is reported to have good conversion and
selectivity (Moreau et al., 2004). The dehydration of glucose to HMF is much
harder than for fructose and thus gives poorer selectivity. However, glucose
can be converted to fructose by the enzyme glucose isomerase. The process
starts with glucose and involves isomerization, dehydration and oxidation to
synthesize FDA. The reaction conditions for the three main reactions are listed
in Table 1.

There
are many alternative options and technologies in the route from glucose to FDA.
One option is to run the three individual reactions separately. Even in this
way, there are many options. For example, the second reaction involving
dehydration fructose to HMF can be running in different media like water,
organic solvent, biphasic system or ionic liquid (Kuster, 1990; Zhao et al.,
2007). Furthermore, the dehydration reaction and the oxidation reaction can
also be integrated together (Kröger et al., 2000). All the possible process
alternatives thus give a big challenge for design engineers, especially at the
early stage of the process design.

In
this paper, the use of a computer-aided model framework to design and select a
suitable scaleable process from glucose to FDA within economic
constraints is described as an example to illustrate how to use the
methodology. The complexity, challenges and opportunities in
chemo-enzymatic process design are also emphasized. The methodology behind
should be applied to a large range of chemo-enzymatic synthesis problems. In
addition, it is also an example to show that computer aided modeling provides a
testing ground for process design.

Table 1: Typical reaction conditions for three main reactions
involved in synthesis FDA.

REFERENCES

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