Biosynthesis of Ester-Bond Containing Quinolone Alkaloids with (3R,4S) Stereoconfiguration.

Asperalins represent a novel class of viridicatin natural products with potent inhibitory activities against fish pathogens. In this study, we elucidated the biosynthesis of asperalins in the Aspergillus oryzae NSAR1 heterologous host and identified the FAD-dependent monooxygenase AplB stereoselectively hydroxylates viridicatin to yield a unique 3R,4S configuration. The monomodular NRPS AplJ catalyzes a rare intramolecular ester bond formation reaction using dihydroquinoline as a nucleophile. Subsequent modifications by cytochrome P450 AplF, chlorinase AplN, and prenyltransferase AplE tailor the anthranilic acid portion, leading to the formation of asperalins. Additionally, we explored the potential of AplB for the hydroxylation of viridicatin analogs, demonstrating its relaxed substrate specificity. This finding suggests that AplB could be developed as a biocatalyst for the synthesis of viridicatin derivatives.

Major Facilitator Superfamily Transporter Participates in the Formation of Dimeric Sorbicillinoids Pigments.

Understanding the biosynthetic pathways of fungal pigments can help elucidate their roles in fungal growth processes. Trichodimerol is a unique cage-like dimeric sorbicillinoids pigment that is commonly isolated from many fungi, however, its biosynthesis is just partially clarified. In this study, we report that a biosynthetic gene cluster encoded major facilitator superfamily transporter (StaE) from the fungus Stagonospora sp. SYSU-MS7888 is involved in the formation of trichodimerol, together with several other dimeric sorbicillinoids. Using Aspergillus oryzae NSARI as a heterologous host, we demonstrated that the formation of dimeric sorbicillinoids required co-expression of the transporter StaE with biosynthetic genes (two PKSs and one monooxygenase) that are responsible for constructing the monomer precursor sorbicillinol. Fluorescence microscopy results showed that eGFP-tagged StaE is localized on the endoplasmic reticulum, suggesting that sorbicillinoid dimerizations might be compartmentalized in this organelle.

Anticancer fungal natural products: Mechanisms of action and biosynthesis.

Many fungal metabolites show promising anticancer properties both in vitro and in animal models, and some synthetic analogs of those metabolites have progressed into clinical trials. However, currently, there are still no fungi-derived agents approved as anticancer drugs. Two potential reasons could be envisioned: 1) lacking a clear understanding of their anticancer mechanism of action, 2) unable to supply enough materials to support the preclinical and clinic developments. In this review, we will summarize recent efforts on elucidating the anticancer mechanisms and biosynthetic pathways of several promising anticancer fungal natural products.

Direct Arylation of Pyrroles via Indirect Electroreductive C-H Functionalization Using Perylene Bisimide as an Electron-Transfer Mediator.

The indirect electroreductive coupling of aryl halides and pyrroles was successfully conducted using a catalytic amount of perylene bisimide as a mediator in 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide ([EMIM]NTf2)/DMSO.