Biosynthetic Pathway Engineering and Discovery
Microbes and plants synthesize a tremendous diversity of chemical compounds that is unmatched by synthetic methods. We are interested in exploring and utilizing the metabolic machineries of plants and microorganisms to enable the discovery and synthesis of valuable compounds in recombinant microbial hosts. We combine enzyme functions obtained from different sources into new metabolic reactions sequences for desired compounds. We use both protein structure guided and in vitro evolution strategies to alter and optimize the catalytic function of enzymes in assembled pathways. In addition to the engineering of metabolic machineries, a major focus of our research is also directed at understanding the functions and catalytic activities of the biosynthetic enzymes and from there generate a better understanding of metabolic pathways. Currently we investigate and engineer the biosynthesis of diverse isoprenoid- and phenylpropanoid-derived compounds.
Engineering of Complex Metabolic Functions
We are also interested in incorporating in a heterologous microbial host more complex metabolic functions than pathways to eventually generate designer bacteria with new useful properties. Currently we are exploring ways of introducing light-converting mechanisms into non-photosynthetic/phototrophic bacteria for the conversion of solar energy into useful metabolic outputs. Other projects deal with the design of genetic circuits for biofuel production and engineering of microbial cell-cell communication.
Biosynthesis and Designer Microbes
The still largely unexplored structural and chemical diversity of natural products is unmatched by synthetic method and continues to be the most successful source for the discovery of novel scaffolds with important biological activities. We are exploiting and investigating the selectivity and specificity of the biosynthetic machineries that make these complex compounds to create ways of synthesizing diverse natural products or their core scaffolds for further synthetic modification. To do so, we are fitting microbial cells with new biosynthetic abilities using metabolic and genetic pathway engineering strategies together with evolutionary and rational protein engineering strategies to alter and study biosynthetic activities. The ability to rapidly assemble genetic components and synthesize DNA cheaply allows the redesign of biological systems for the execution of new functions. We introduce complex new metabolic abilities into microbial cells to generate designer bacteria with useful new properties.
Johnson ET, Baron DB, Naranjo B, Bond DR, Schmidt-Dannert C, Gralnick JA (2010) Enhancement of survival and electricity production in an engineered bacterium by light-driven proton pumping. Appl Environ Microbiol. 76:4123-9. PMID: 20453141
Lopez-Gallego F, Agger SA, Abate-Pella D, Distefano MD, Schmidt-Dannert C (2010) Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. Chembiochem. 11:1093-106. PMID: 20419721
Choudhary S, Schmidt-Dannert C (2010) Applications of quorum sensing in biotechnology. Appl Microbiol Biotechnol. 86:1267-79.PMID: 20306190
Lopez-Gallego F, Schmidt-Dannert C. (2010) Multi-enzymatic synthesis. Curr Opin Chem Biol. 14:174-83. PMID: 20036183
Agger S, Lopez-Gallego F, Schmidt-Dannert C (2009) Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol Microbiol. 72:1181-95. PMID: 19400802.
Johnson ET, Schmidt-Dannert C (2008) Light-energy conversion in engineered microorganisms. Trends Biotechnol. 26:682-9. PMID: 18951642
Agger SA, Lopez-Gallego F, Hoye TR, Schmidt-Dannert C (2008) Identification of sesquiterpene synthases from Nostoc punctiforme PCC 73102 and Nostoc sp. strain PCC 7120. J Bacteriol. 190:6084-96. PMID: 18658271
Holtzapple E, Schmidt-Dannert C (2007) Biosynthesis of isoprenoid wax ester in Marinobacter hydrocarbonoclasticus DSM 8798: identification and characterization of isoprenoid coenzyme A synthetase and wax ester synthases. J Bacteriol. 189:3804-12. PMID: 17351040
Watts KT, Mijts BN, Lee PC, Manning AJ, Schmidt-Dannert C (2006) Discovery of a substrate selectivity switch in tyrosine ammonia-lyase, a member of the aromatic amino acid lyase family. Chem Biol. 13:1317-26. PMID: 17185227
Marasco EK, Vay K, Schmidt-Dannert C (2006) Identification of carotenoid cleavage dioxygenases from Nostoc sp. PCC 7120 with different cleavage activities. J Biol Chem. 281:31583-93. PMID: 16920703