Back to ambergris – clary sage is easier to get hold of than whale faeces, but even so the herb contains only tiny amounts of sclareol, and it is laborious to extract and purify. That’s why Firmenich’s Michel Schalk and his colleagues wanted to see if they could take the sclareol-producing genes from the herb and put them in the gut bacterium Escherichia coli, the ubiquitous single-celled workhorse used by the biotechnology industry for cloning genes and expressing therapeutically useful products.
Sclareol belongs to a class of organic compounds called terpenes, many of which are strong-smelling and are key components of the essential-oil extracts of plants. Sclareol contains two rings of six carbon atoms each, formed when enzymes called diterpene synthases stitch together parts of a long chain of carbon atoms. The Firmenich researchers show that the formation of sclareol is catalysed in two successive steps by two different enzymes.
Schalk and colleagues extracted and identified the genes that encode these enzymes, and transplanted them into E. coli. That alone, however, doesn’t necessarily make the bacteria capable of producing lots of sclareol. For one thing, it also has to be able to make the long-chained starting compound, which can be achieved by adding yet another gene from a different species of bacteria that happens to produce the stuff naturally.
More challengingly, all of the enzymes have to work in sync, which means giving them genetic switches to regulate their activity. This approach – making sure that the components of a genetic circuit work together like the parts of a machine to produce the desired chemical product – is known as metabolic engineering. This is one level up from genetic engineering, tailoring microorganisms to carry out much more demanding tasks than those possible by simply adding a single gene. It has already been used to make bacteria produce other important natural compounds, such as the anti-malarial drug artemisinin.
With this approach, the Firmenich team was able to create an E. coli strain that could turn cheap, abundant glycerol into significant quantities (about 1.5 grams per litre) of sclareol. So far this has just been done at a small scale in the lab. If it can be scaled up, you might get to smell expensively musky without the expense. Or at least, you would if price did not, in the perfume business, stand for an awful lot more than mere production costs.