Waning resources, massive energy consumption, ever‐deepening global warming crisis, and climate change have raised grave concerns regarding continued dependence on fossil fuels as the predominant source of energy and generated tremendous interest for developing biofuels, which are renewable. Hydrocarbon‐based ′drop‐in′ biofuels can be a proper substitute for fossil fuels such as gasoline or jet fuel. In Nature, hydrocarbons are produced by diverse organisms such as insects, plants, bacteria, and cyanobacteria. Metalloenzymes play a crucial role in hydrocarbons biosynthesis, and the past decade has witnessed discoveries of a number of metalloenzymes catalyzing hydrocarbon biosynthesis from fatty acids and their derivatives employing unprecedented mechanisms. These discoveries elucidated the enigma related to the divergent chemistries involved in the catalytic mechanisms of these metalloenzymes. There is substantial diversity in the structure, mode of action, cofactor requirement, and substrate scope among these metalloenzymes. Detailed structural analysis along with mutational studies of some of these enzymes have contributed significantly to identifying the key amino acid residues that dictate substrate specificity and catalytic intricacy. In this Review, we discuss the metalloenzymes that catalyze fatty acid‐derived hydrocarbon biosynthesis in various organisms, emphasizing the active site architecture, catalytic mechanism, cofactor requirements, and substrate specificity of these enzymes. Understanding such details is essential for successfully implementing these enzymes in emergent biofuel research through protein engineering and synthetic biology approaches.

Hydrocarbon biosynthesis has gained tremendous attention in recent years due to its implication in the development of next‐generation advanced biofuels. In nature, various organisms such as plants, insects, bacteria, and cyanobacteria produce fatty acid‐derived alka(e)nes. Most of the enzymes involved in fatty acid‐derived hydrocarbon biosynthesis are metalloenzymes, which employ divergent and intriguing catalytic mechanisms. Herein, metalloenzymes are reviewed in detail with special emphasis on their structure and mechanism. More information can be found in the Review by Debasis Das et al.