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Abstract As a promising industrial microorganism, methylotroph is capable of using methane or methanol as the sole carbon source natively, which has been utilized in the biosynthesis of various bioproducts. However, the relatively low efficiency of carbon conversion has become a limiting factor throughout the development of methanotrophic cell factories due to the unclear genetic background. To better highlight their advantages in methane or methanol-based biomanufacturing, some metabolic engineering strategies, including upstream transcription regulation projects, are being popularized in methylotrophs. In this review, several strategies of transcription regulations applied in methylotrophs are summarized and their applications are discussed and prospected.