Comparative modeling is becoming an increasingly helpful technique in microbial cell factories as the knowledge of the three-dimensional structure of a protein would be an invaluable aid to solve problems on protein production.
For this reason, an introduction to comparative modeling is presented, with special emphasis on the basic concepts, opportunities and challenges of protein structure prediction.
However, bacterial organisms often fail to produce target proteins due to problems related with protein misfolding and protein glycosilation.
Yeast and fungal protein expression systems are used for the industrial production of relevant enzymes in such cases .
All current comparative modeling methods consist of four sequential steps: template selection, target-template alignment, model building and model evaluation.
Essentially, this is an iterative procedure until a satisfactory model is obtained (Figure 1).Our goal is to provide the seeding background to understand concepts, opportunities and challenges of comparative modeling.We will describe each step in the comparative modeling process, discuss the most common errors and how to solve them, as well as outlining the applications of comparative modeling in the field of microbial cell factories.Programs and servers referring to these steps are listed in table 1.The starting point in comparative modelling is to identify protein structures related to the target sequence and then to select those that will be used as templates.Even though, below that threshold structural likeness is still possible.Some protein pairs sharing very little sequence similarity may have become similar by convergent or divergent evolution.This review is intended to serve as a guide for the biologist who has no special expertise and who is not involved in the determination of protein structure.Selected applications of comparative modeling in microbial cell factories are outlined, and the role of microbial cell factories in the structural genomics initiative is discussed.Such templates may be found by sequence comparison methods or by sequence-structure methods also known as threading methods.Sequence comparison methods can be safely used above a certain threshold in terms of sequence identity (i.e.