Integration of sequence and reaction data for the design and engineering of methionine adenosyltransferases and other SAM–dependent enzymes

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In this project P8, an integrated computational platform for analysing data on sequence, structure, and function of enzymes will be developed and applied to design tailored methionine adenosyltransferases (MATs) with an altered substrate profile. In cells, MATs produce S adenosylmethionine (SAM) from 5´-adenosine triphosphate (ATP) and L-methionine. The target for the envisioned enzyme variants is the control of the enzyme’s discrimination of L- and D-methionine. In addition to selective variants, also unselective variants will be designed and characterised. The integrated platform will be developed alongside the MAT project and comprises bioinformatics workflows and a research data management toolbox for biocatalytic data. The bioinformatics workflows are applied for studying sequence-function relationships, finding new enzyme candidates in sequence databases, and designing highly enriched mutant libraries. The research data management toolbox is based on the standardised data exchange format EnzymeML and is applied for managing, analysing, and publishing experimental and modelling results according to the FAIR data principles. The platform development is a collaborative project using existing tools such as GitHub, Jupyter, the Biopython library, and Galaxy, and incorporates existing databases, formats, and standards. The platform is used by all FOR partners, who will be enabled to install it locally, adapt it to their needs, and apply if for analyzing and publishing their data and for sharing methods and results. The computational tools developed in P8 are reusable and extensible, the workflows enable reproducibility of data analysis, and the use of standardized formats make results interoperable. The tools developed in P8 focus to the needs of the FOR but can be extended and generalized beyond this FOR and thus contribute to the digitalization of (bio)catalytic sciences.