<jats:title>ABSTRACT</jats:title> <jats:p> Lantibiotics are antimicrobial peptides belonging to the family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and feature thioether linkages in their structures. In this study, we identified the biosynthetic gene cluster of a cinnamycin analog, named mathermycin, from <jats:named-content content-type="genus-species">Marinactinospora thermotolerans</jats:named-content> SCSIO 00652 and reconstituted its biosynthesis in <jats:named-content content-type="genus-species">Streptomyces lividans</jats:named-content> and <jats:named-content content-type="genus-species">Escherichia coli</jats:named-content> . Key posttranslational modification enzymes of mathermycin were characterized. Mathermycin exhibited antimicrobial activity and therefore represents an example of cinnamycin-like lantibiotics from <jats:named-content content-type="genus-species">Marinactinospora</jats:named-content> species. <jats:p> <jats:bold>IMPORTANCE</jats:bold> The discovery of new antimicrobial compounds that can be used as potential drugs is in urgent need due to increasing bacterial resistance to current antibiotics. Lantibiotics are important antimicrobial compounds that have found applications in both the clinic setting and food industry. We report here the discovery of a new lantibiotic, mathermycin, from a marine-derived <jats:named-content content-type="genus-species">Marinactinospora thermotolerans</jats:named-content> strain and elucidation of its biosynthesis. We also demonstrate that mathermycin possesses antimicrobial activity toward a <jats:named-content content-type="genus-species">Bacillus</jats:named-content> strain.