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NextProd

Industrial production of protein based products such as enzymes and pharmaceutical proteins is carried out in cell factories, organisms optimized to provide maximum yield through fine tuned adjustment of their metabolism. Even modest increases in the yield will have large societal value, not only in form of cheaper products (such as food, consumer products and drugs) and bigger earnings, but will also significantly contribute to a more sustainable and a green production. Improvement of cell factories therefore holds a large potential for growth on the long run. owever, traditional optimization techniques, based on the class of genes encoding proteins, have been applied to such an extent that real improvements no longer seem realistic despite that current protein yields are significantly below the theoretical carbon yield. Conversely, the often ignored class of genes not coding for proteins, the non-coding RNAs (ncRNAs) have not been explored for optimization and thus hold a completely untouched potential, in part because ncRNA often is involved in regulation.

Research

The goal of the project is to construct next generation cell factories based on manipulation of ncRNAs. This will be accomplished by combining computational and experimental techniques to comprehensively characterize ncRNAs in different strains of Bacillus subtilis, which is an important production organism. The computational approach will provide an in depth annotation for known ncRNA genes and RNA structural regulatory elements (of which some may be located on transcripts of protein coding genes) as well as a thorough map of de novo predicted (structured) ncRNAs. The experimental approach will provide ncRNA expression data and an RNA structure profile (by a high-throughput SHAPE-seq strategy) for each of the strains. The ncRNA data will be correlated to the yield of the different strains to identify ncRNAs that are good candidates for affecting yield. These ncRNAs will then be screened in an assay resembling a real production set-up to identify the ncRNAs that can be used to improve yield. The next step is to propagate these into an industrial development flow with the aim of testing and preparing for actual industrial application. In addition, the project will make the settings, tools etc available to be freely used for development of next generation cell factories from other expression systems, e.g. those based on Aspergillus.

Publications

INTERNAL

© Center for non-coding RNA in Technology and Health