# Whole-cell modeling predicts alternative proteome allocation strategies in the archaeon Methanococcus maripaludis

## TL;DR

A new model explains how the archaeon Methanococcus maripaludis allocates its proteome resources during growth.

## Contribution

A proteome-constrained metabolic model is developed to explain unique proteome allocation in Methanococcus maripaludis.

## Key findings

- The model explains why ribosomal proteome allocations remain constant with growth rates in M. maripaludis.
- The model predicts alternative proteome allocation strategies and mutant fitness under different conditions.
- The model provides a framework for studying resource allocation in hydrogenotrophic methanogenesis.

## Abstract

The archaeon Methanococcus maripaludis (M. maripaludis) is a model organism for studying archaeal physiology and energy conservation in the hydrogenotrophic methanogenesis pathway. M. maripaludis has a distinct proteome allocation strategy, in which ribosomal proteome allocations do not change with growth rates. Here, we developed a proteome-constrained metabolic model that can explain this different proteome allocation strategy. First, we used multiple bioinformatics databases to compile information about the translational process and enzymatic complexes. We then extended a genome-scale metabolic model of M. maripaludis with protein synthesis processes, including ribosome assembly, tRNA charging, and enzyme assembly reactions. The proposed model predicts alternative proteome resource allocation strategies and mutant fitness for this archaeon under different conditions. Therefore, our model provides a framework for studying the effects of resource allocation on the hydrogenotrophic methanogenesis pathway.

The online version contains supplementary material available at 10.1038/s41598-026-37887-z.