Ambergris is a rare, precious substance craved by the perfume industry, but scientists hope they can engineer bacteria to produce the much-coveted fragrance.



But vats of genetically modified bacteria could one day be producing the expensive aromatic chemical craved by the perfume industry, if research reported by biochemists at the Swiss fragrance and flavourings company Firmenich in Geneva comes to fruition. Their results are another demonstration that rare and valuable complex chemicals, including drugs and fuels, can be produced by sophisticated genetic engineering methods that convert bacteria into microscopic manufacturing plants.


Because ambergris needs this period of maturation in the open air, it couldn’t be harvested from live sperm whales even in the days when hunting was sanctioned. It could be found occasionally in whale carcasses – in Moby Dick the Pequod’s crew trick a French whaler into abandoning a whale corpse so that they can capture its ambergris. But most finds are fortuitous, and as was reported recently large pieces of ambergris washed ashore can be worth many thousands of dollars.


Making scents


This is par for the course in the baffling world of the human sense of smell, or as scientists call it, olfaction. In this case Ambrox has a very similar structure to the main smelly molecules in ambergris, but this doesn’t always have to be so: two odorant molecules can smell almost identical while having very different molecular structures (they are all generally based on frameworks of carbon atoms linked into rings and chains). Equally, two molecules that are almost identical, even mirror images of one another, can have very different odours. Quite how such molecules elicit a smell when they bind to the proteins in the olfactory membrane of the nasal cavity is still not understood.

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.


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.

