Enhancement of the viability of T cells electroporated with DNA via osmotic dampening of the DNA-sensing cGAS-STING pathway.

Viral delivery of DNA for the targeted reprogramming of human T cells can lead to random genomic integration, and electroporation is inefficient and can be toxic. Here we show that electroporation-induced toxicity in primary human T cells is mediated by the cytosolic pathway cGAS-STING (cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase-stimulator of interferon genes). We also show that an isotonic buffer, identified by screening electroporation conditions, that reduces cGAS-STING surveillance allowed for the production of chimaeric antigen receptor (CAR) T cells with up to 20-fold higher CAR T cell numbers than standard electroporation and with higher antitumour activity in vivo than lentivirally generated CAR T cells.

Metabolites from carnivorous fungus Arthrobotrys entomopaga and their functional roles in fungal predatory ability.

The carnivorous fungus Arthrobotrys entomopaga (Drechsler) can develop adhesive knobs to capture nematodes. Chemical study on the culture medium of A. entomopaga producing adhesive knobs led to isolation of six trace amounts of metabolites, including two new metabolites, paganins A and B (1 and 2), blumenol A (3), talathermophilins A and B (4 and 5), and cyclo(glycyltryptophyl) (6).

Thermolides, potent nematocidal PKS-NRPS hybrid metabolites from thermophilic fungus Talaromyces thermophilus.

Macrocyclic PKS-NRPS hybrid metabolites represent a unique family of natural products mainly from bacteria with broad and outstanding biological activities. However, their distribution in fungi has rarely been reported, and little has been reported regarding their nematocidal activity. Here we describe an unprecedented class of PKS-NRPS hybrid metabolites possessing a 13-membered lactam-bearing macrolactone, thermolides A-F (1-6) from a thermophilic fungus Talaromyces thermophilus.

Morphology regulatory metabolites from Arthrobotrys oligospora.

Novel autoregulatory metabolites, arthrosporols A-C (1-3), involved in regulating the morphological switch in fungi, were purified and characterized from the carnivorous fungus Arthrobotrys oligospora. These compounds possess a novel hybrid carbon skeleton consisting of an epoxy-cyclohexenol combined with a rare monocyclic sesquiterpenol substructure. This is the first report of a monocyclic sesquiterpenol of this type of fungal origin.

Isolation of talathermophilins from the thermophilic fungus Talaromyces thermophilus YM3-4.

Six indole alkaloids with various levels of prenylation were isolated from the thermophilic fungus Talaromyces thermophilus strain YM3-4. Their structures were identified by NMR and MS spectroscopic analyses. Compounds 1 and 2 are new analogues of the key versatile precursor notoamide E.