The fungi used in biopharmaceuticals’ vat fermentation process may soon have an additional feedstock option: polyethylene. In a report in Angewandte Chemie, researchers at the University of Southern California (USC) used polyethylene gathered from Catalina Island’s main harbor as the feedstock for genetically-engineered Aspergillus nidulans. That filamentous fungi then then synthesized useful quantities of asperbenzaldehyde, citreoviridin, and mutilin natural products, which are precursors for a variety of therapeutic agents.
The USC team catalytically converted the polyethylene to make carboxylic diacids. Unlike some other upcycling approaches, the oxidative process tolerates the impurities associated with post-consumer waste, including salt, the authors explained.
Then, they removed the diacids that had less than ten carbon atoms. (Those short-chains are toxic to A. nidulans, but they can be used to produce biodegradable plastics for agriculture.) For biopharma manufacturing, it’s the longer-chain diacids–specifically, those with 10 and 12 carbons–that are valuable. They were fed to the A. nidulans that had been engineered to overexpress secondary metabolite biosynthetic genes or gene clusters.
Higher yield of secondary metabolites
“The fungi make a much higher yield of secondary metabolites (such as antibiotics) when fed plastic digest than when fed glucose under analogous conditions,” Travis J. Williams, PhD, one of the authors, tells GEN. For example, the highest yielding strain of those grown in liquid lactose minimal media inside shake flasks had a 29 percent conversion of lactose to asperbenzaldehyde in less than one week. Williams and colleagues suggest that even higher yields may be obtained by altering other culture parameters, such as media or culture time.
“I think (the higher yields are) because the funny food source stresses them, so they’re putting out toxins, preparing to go to spore,” Williams speculated. Initially, the high-yielding strain grew slower than the control strain. After 48 hours, however, the growth of the fungal fragments (hyphal) was considered amble and, after 72 hours, abundant asperbenzaldehyde crystals were seen.
Next, Williams says, “We want to show that we can process mixed plastics waste without sorting…and to diversify our product portfolio.” It seems likely that this method can be used to produce proteins, organic acids or other fermentation products. Another paper, currently being peer reviewed, addresses those points, he adds.
Before this method can be inserted into the drug manufacturing sequence, additional process development is needed. But, Williams notes, “I don’t see hurdles that can’t be addressed. I think we’re a year or so from market if we find an enthusiastic and capable partner.”
