Structural highlights
Publication Abstract from PubMedMalonyl-CoA and methylmalonyl-CoA are two of the most commonly used extender units for polyketide biosynthesis, and are utilized to synthesize a vast array of pharmaceutically relevant products with antibacterial, antiparasitic, anticholesterol, anticancer, antifungal, and immunosuppressive properties. Heterologous hosts used for polyketide production such as Escherichia coli often do not produce significant amounts of methylmalonyl-CoA, however, requiring the introduction of other pathways for the generation of this important building block. Recently the bacterial malonyl-CoA synthetase class of enzymes has been utilized to generate malonyl-CoA and methylmalonyl-CoA directly from malonate and methylmalonate. We demonstrate that in the purple photosynthetic bacterium Rhodopseudomonas palustris MatB (RpMatB) acts as a methylmalonyl-CoA synthetase and is required for growth on methylmalonate. We report the apo (1.7 A resolution) and ATP bound (2.0 A resolution) structure and kinetic analysis of RpMatB, which shows similar activity for both malonate and methylmalonate, making it an ideal enzyme for heterologous polyketide biosynthesis. Additionally, rational, structure-based mutagenesis of the active site of RpMatB led to substantially higher activity with ethylmalonate and butylmalonate, demonstrating that this enzyme is a prime target for expanded substrate specificity. Structure-guided expansion of the substrate range of methylmalonyl-CoA synthetase (MatB) of Rhodopseudomonas palustris.,Crosby HA, Rank KC, Rayment I, Escalante-Semerena JC Appl Environ Microbiol. 2012 Jul 6. PMID:22773649[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||||
This page was last modified 07:32, 15 February 2015.