Abstract
Ambergris is a very rare and highly valued fauna natural perfume. Its main component, ambrein, undergoes oxidative degradation to produce ambroxide, forming the unique ambergris fragrance. To meet the market demand while not offending the law of protecting sperm whales, ambrein and ambroxide are chemically synthesized. Recently, the biosynthesis of these compounds has been explored as a green and sustainable production route to ensure the safety of use. The ambrein biosynthesis pathway has been successfully constructed in model microorganisms, leading to de novo biosynthesis of ambrein from glucose and glycerol. In addition, partial biosynthesis of ambroxide has been achieved by modular co-culture of engineered sclareol-producing yeast and a natural fungus converting sclareol to ambradiol, which can be further converted to ambroxide by zeolite. Alternatively, ambroxide can be produced by the chemical transformation of biosynthesized farnesene, followed by enzymatic cyclization. In this paper, the efforts toward biosynthesis of ambrein and ambroxide as representative compounds to substitute the natural ambergris are reviewed, and the challenges and prospects are discussed.