lecture9 - 10.492 Integrated Chemical Engineering(ICE...

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Lecture #9 – Biological Solutions to Process Design Problems Handout: (1) Burton et al paper [ Nature Biotech . (2002). 20 :37-45], (2) Biological Solutions grid, (3) Case Studies cont. handouts (three) We previously discussed a series of process design challenges and defined them as either engineering or biological. We also discussed engineering solutions to those problems. Over the next few lectures, and to wrap-up the course, we’ll talk about biological solutions to some of those problems and to the others that we have not yet discussed. Problem/Solutions Grid Engineering Solution Biological Solution Engineering Problem Yes No (*1 case exception) Biological Problem Yes Yes Note that engineering problems, based on how we’ve defined them, cannot be solved by a biological resolution because they were concerned with physico-chemical or thermodynamic aspects of the substrates/products. * There is one exception here. We might consider improvement of equilibrium reactions by coupling product removal to a second reaction to be a biological solution if we use a second enzyme. However, if we simply add a free enzyme, we haven’t really changed our initial catalyst, so our definition of a biological solution isn’t valid. It is valid if we alter a whole cell catalyst. Likewise, some biological problems cannot be resolved with an engineering solution. All biological problems, however, can potentially be addressed with biological solutions. The biological challenges we’ve discussed so far include the following: Enzyme instability (could be as a function of reaction conditions, like pH) Substrate inhibition/toxicity Product inhibition/toxicity By-product formation The following enzyme-specific issues were also on your handout as having only biological solutions: Low enzyme activity Wrong or limited substrate specificity Poor selectivity 10.492 - Integrated Chemical Engineering (ICE) Topics: Biocatalysis MIT Chemical Engineering Department Instructor: Professor Kristala Prather Fall 2004 Dr. Kristala L. Jones Prather, Copyright 2004. MIT Department of Chemical Engineering
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Lecture #9, p.2 Each of these problems can be addressed by altering the catalyst, whether it is a free enzyme or a whole cell. 1. Characteristics of biological solutions Recall that we defined a biological problem as one being specifically related to the nature of the catalyst. For the purposes of this discussion, we’ll assume that simply screening for a better catalyst is not an option to our biological problems. So, once we’ve exhausted engineering solutions, we can turn to biological solutions for a remedy. Our objective now is to alter the existing catalyst to make it better. We can do this for either purified enzymes or whole cells, and we can use a random or a rational approach (see chart below). In this case, a random approach is defined as one in which you make many different versions of your base catalyst and then use screening in order to find an improved variant. A rational approach implies that a targeted, specific change was made to the catalyst in order to obtain an improved enzyme or whole cell.
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lecture9 - 10.492 Integrated Chemical Engineering(ICE...

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