Given the usefulness of GSMMs, efforts have been made to accelerate extensive and time-consuming tasks of the reconstruction process. Nevertheless, reconstructing high-quality curated models is often time-consuming and laborious, as it can take from a few months to years ( 3). Correspondingly, the production of curated GSMMs has taken the pace, achieving the mark of six thousand since 1999’s Haemophilus influenzae's model publication ( 1). Over the past two decades, an increasing number of genome sequences have become available ( 2). Such models have been guiding metabolic engineering towards maximizing cell factories’ efficiency, predicting the most suitable conditions for driving flux into the production of compounds of interest. Within their broad spectrum of applications ( 1), high-quality GSMMs can be used to predict phenotypes under different genetic and environmental conditions. Accordingly, the metabolic information inferred from the genome is integrated with biochemical data, commonly retrieved from reference databases. Genome-scale metabolic models (GSMMs) are genome-wide representations of a given organism's metabolism. merlin version 4.0 is the only tool able to perform template based and de novo draft reconstructions, while achieving competitive performance compared to state-of-the art tools both for well and less-studied organisms. Such updates increased the user base, resulting in multiple published works, including genome metabolic (re-)annotations and model reconstructions of multiple (lower and higher) eukaryotes and prokaryotes. The current version (4.0) includes the implementation of novel algorithms and third-party tools for genome functional annotation, draft assembly, model refinement, and curation. Since 2015, several features have been implemented in merlin, along with deep changes in the software architecture, operational flow, and graphical interface. An updated and redesigned version of merlin is herein presented. merlin ( ) is an open-source and user-friendly resource that hastens the models’ reconstruction process, conjugating manual and automatic procedures, while leveraging the user's expertise with a curation-oriented graphical interface. Genome-scale metabolic models have been recognised as useful tools for better understanding living organisms’ metabolism.
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