HotHouse Therapeutics remixes plant compound biosynthesis for pharma

HotHouse Therapeutics has emerged from stealth with a little over $3 million in preseed funding. The start-up, based in Norwich, England, mixes artificial intelligence and synthetic biology to reprogram plant biosynthetic pathways to create new molecules.“Synthetic chemistry is not delivering new therapeutics at the rate that it needs to . . . whereas plants are chemical engineers par excellence, and they make a huge array of diverse chemistry,” says Anne Osbourn, HotHouse’s chief science officer and a natural product biologist at the John Innes Centre.One of Osbourn’s recent academic achievements was elucidating the entire biosynthetic pathway for the vaccine adjuvant QS-21—a compound now obtained mainly from the soapbark tree, which is native to central Chile (Science 2023, DOI: 10.1126/science.adf3727).QS-21, which helps stimulate the immune system, is a component of the Shingrix shingles vaccine, among other vaccines But the difficulty of sourcing soapbark and extracting QS-21 has made the compound expensive, prompting several start-ups to try to produce it by other means.HotHouse is using Osbourn’s knowledge of the QS-21 pathway to make the molecule in Nicotiana benthamiana, a relative of tobacco often used in plant biotechnology. The firm is also leveraging its AI platform to tweak the pathway to create related molecules.According to Osbourn, QS-21 is far from a perfect adjuvant. “It is a potent immunostimulant, but it's quite toxic to human cells,” she says. HotHouse is hoping pharmaceutical companies will test their products on the related molecules to find an ideal adjuvant for their purposes.But CEO David Sheppard doesn’t want