Researchers finally provide a blow-by-blow account of the biosynthesis of cocaine. For over a century, scientists have sought to devise a method to quickly and cheaply synthesize massive amounts of cocaine, yet had until now been baffled by the drug’s mysterious biochemistry. However, the authors of a new study appear to have finally cracked the conundrum by genetically altering a type of tobacco plant to produce the white stuff. Naturally occurring in the coca plant, cocaine is a tropane alkaloid that is as notorious for its potential for abuse as it is interesting to medical scientists. In the 19th century, for instance, the stimulant was successfully used as an anesthetic for eye surgery. More recently, the US Food and Drug Administration (FDA) approved the use of cocaine as a topical anesthesia of mucous membranes. However, in order to learn more about the stimulant’s medicinal properties, researchers first have to get to grips with its biosynthesis. Previously, scientists have attempted to learn more about this by studying a similar tropane alkaloid called hyoscyamine, which, like cocaine, is created from the chemical precursor 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid – or MPOA for short. In the synthesis of hyoscyamine, MPOA is converted to methyl 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoate (MMPO), leading to the assumption that the same pathway must be involved in cocaine production. However, previous studies have failed to illuminate how this process gives rise to cocaine. Solving the riddle, the authors of the new study reveal that, unlike hyoscyamine, marching powder is not produced from MMPO. Instead, MPOA is converted into cocaine thanks to the activity of two enzymes called EnCYP81AN15 and EnMT4. To prove it, the researchers genetically altered a relative of the tobacco plant to produce these two enzymes, resulting in the synthesis of cocaine in the plant’s leaves. And while the amount produced was far lower than that seen in coca plants, the fact that the biosynthesis of cocaine has now been unlocked opens up the possibility of mass-producing the drug in other organisms such as E. coli. As dangerous as this sounds, the study authors’ breakthrough is unlikely to have any impact on the illicit cocaine trade, as the process of genetically altering another plant or microbe to synthesize the drug is far beyond the capabilities of even the most sophisticated cartels. However, this work may lay the foundations for more detailed studies of cocaine and its derivatives, leading to new insights into how compounds related to blow might be of medical use. Source
