Richard W. Dapson writes, on 17th May 2021:

Carminic acid and its aluminum lake, carmine, are important histological dyes, but commercial trade in these products has undergone massive shifts in the last few decades due to market forces way beyond histology. Originally a textile dye from Central and South America, indigenous people harvested a parasitic bug (Dactylopius coccus) from prickly pear cacti (Opuntia), dried and ground them, then extracted the dye, carminic acid. Over a few thousand years, these people had practiced artificial selection, choosing the most robust cacti and the most prolific bugs to maximize dye yields. Somewhere along the way the red dye was incorporated into foods and beverages like today’s strawberry milk, candies, ketchup and various cosmetics (lipstick, eye shadow and nail polish), even while the use for textile dyeing almost ceased. Large plantations were established in Chile, Peru and the Canary Islands decades ago. But despite all of that, current demand has greatly outstripped supply. Natural production cannot be ramped up significantly. Habitat for cacti is limited, growth of both host and parasite are slow and extraction procedures are woefully inefficient. Yields are astonishingly low: 1 pound of dye extracted from 70,000 cochineal insects that were hand picked from spiny cacti!

There is now a new process, thanks to innovations in genetic engineering. Scientists in the Republic of Korea have successfully modified the genome of the bacterium Escherichia coli, adding genes from other organisms to create enzymes not normally found in E. coli. Attempts to transfer genes directly from the cochineal insect to the bacterium were not successful, so a novel synthetic pathway was created. These enzymes direct a multi-step synthesis of carminic acid from glucose, not at all the starting point for cochineal bugs, but who said you had to follow the rules of nature? The improvement in efficiency is astounding. A 100,000 liter fermentation vat produces in about 5 days what can be extracted from each hectare of cactus planation per year! And the vagaries of climate, geopolitics and labor issues are conveniently absent. Information for this article was taken from Yang D, Jang WD, Lee SY (2021) Production of carminic acid by metabolically engineered Escherichia coli. J. Amer. Chem. Soc. 143: 5364-5377. For a lengthy review of the natural and geopolitical history, production techniques, chemistry and histochemistry, see Dapson RW (2007) The history, chemistry and modes of action of carmine and related dyes. Biotech. Histochem. 82: 173-187.