The growing demand for sustainable biomanufacturing has increased interest in nonfood, low-cost carbon feedstocks, particularly methanol and mannitol, owing to their availability and high energy density. However, conventional model microorganisms often show limited efficiency and robustness on such substrates, motivating the exploration of alternative chassis. This review highlights Bacillus methanolicus as an emerging biomanufacturing platform capable of efficiently utilizing both methanol and mannitol. Its thermophilic growth, seawater adaptation, and energy-efficient methanol assimilation pathway provide intrinsic advantages for resource-efficient fermentation processes. We summarize current insights into methanol and mannitol metabolism in B. methanolicus, highlighting that regulation of methanol oxidation and formaldehyde detoxification determines efficient co-utilization, as well as recent advances in synthetic biology tools development that enable rational strain engineering. Finally, we discuss challenges in biomanufacturing from methanol and mannitol, and outline future directions toward establishing B. methanolicus as a versatile platform connecting one-carbon and marine-derived substrates to sustainable chemical synthesis.
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