Methane is a promising carbon feedstock for industrial biomanufacturing because of its low price and high abundance. Recent advances in metabolic engineering and systems biology in methanotrophs have made it possible to produce a variety of value-added compounds from methane, including secondary metabolites. Isoprenoids are one of the largest family of secondary metabolites and have many useful industrial applications. In this review, we highlight the current efforts invested to methanotrophs for the production of isoprenoids and other secondary metabolites, including riboflavin and ectoine. The future outlook for improving secondary metabolites production (especially of isoprenoids) using metabolic engineering of methanotrophs is also discussed. gas-to-liquid bioconversion using methanotrophs, such as limited mass transfer rates of methane, low volumetric productivity, and instability of recombinant strains [11].Secondary metabolites produced by plants and microorganisms have many useful biological activities. Among the many secondary metabolites, isoprenoids are the largest family of natural products, with more than 50,000 members identified [12][13][14]. Many isoprenoids have been used in many applications such as pharmaceuticals, nutraceuticals, fragrances, as well as the chemical industry. Additionally, due to the methyl-branched and cyclized hydrocarbon alkene structure, some isoprenoids have attracted more attention for their potential use as advanced biofuels. Plants are the major sources of isoprenoids. However, there are still many limitations for the production of high quantities of natural isoprenoids, including slow growth and tissue-specific biosynthesis, and difficulties in harvesting and extraction [12][13][14]. In contrast, a promising alternative method for isoprenoid production is the reconstruction of isoprenoid biosynthesis pathways from plants into microbes. The application of this approach has been extensively studied on model organisms like Escherichia coli or Saccharomyces cerevisiae for a variety of isoprenoids [12,14]. E. coli and S. cerevisiae are promising hosts since they possess simple genetic backgrounds, high growth rates as well as well-developed genetic tools. For example, high production of isoprenoid-based biofuels has been achieved in the metabolic engineering of microbes via endogenous or heterologous biosynthetic pathways in these hosts. However, the vast majority of these microbe-based isoprenoid production cases rely on sugar-based metabolism, which is likely to increase in the price of isoprenoids produced in large quantity.The use of alternative carbon sources is attractive in industrial biotechnology for isoprenoid production. Furthermore, different type of pathway regulation in different microbes utilizing unusual carbon substrate like methane can play a vital role in metabolic engineering of various microbes including model organisms. Thus, metabolic engineering of methane-utilizing methanotrophs has recently attracted much attention, due to not only cheaper price of...