Flavonoids are a group of secondary metabolites found in many higher plants. The multiple roles of their flavone subclass include protection against UV damage, regulation of auxin transport, and modulation of flower color. In soybean (Glycine max), flavone synthase II (FNS II) is the key enzyme responsible for flavone biosynthesis. Two FNS II genes from soybean cultivar Hefeng 47 were cloned according to basic local alignment search tool (BLAST) contexts using flavone synthase sequences reported in other species. These were named GmFNSII-1 and GmFNSII-2. Sequence alignments showed that the cDNA of GmFNSII-1 was identical to that of CYP93B16, whereas GmFNSII-2 was clearly distinct. Functional assays in yeast (Schizosaccharomyces pombe) suggested that these two enzymes could convert (2S)-naringenin into apigenin. The two GmFNSII genes had similar tissue-specific expression patterns, but GmFNSII-2 was significantly expressed in the roots after treatment with 0.4 M glucose. This demonstrates that the gene plays an important role in the response to defense signals in soybean. RNA interference-mediated suppression of those GmFNSII genes effectively regulated flavone and isoflavone production in hairy roots that arose from soybean cotyledons transformed with Agrobacterium rhizogenes (ATCC15834). Our study also highlights some of the challenges associated with metabolic engineering of plant natural products.

ObjectiveThe protein post-translational modification (PTM) in host cells can be rewritten by bacterial enzymes and represents an unprecedented mechanism in the communication between intestinal flora and the host. AlthoughAkkermansia muciniphilahas been widely investigated as a probiotic and blunts colitis-associated tumourigenesis in mice, there is little understanding regarding whetherA. muciniphilais involved in the PTM of colorectal cancer (CRC). This study investigates whether and howA. muciniphilaengages in the PTM of host CRC.DesignThe secreting extracellular vesicles fromA. muciniphilaand purified Amuc_2172 were used for different tumourigenesis mice models. Amuc_2172-induced immune activity of CD8+cytotoxic T lymphocytes (CTLs) were evaluated in vitro and in vivo. The acetyltransferase activity and downstream target genes of Amuc_2172 were investigated.ResultsAmuc_2172, a general control non-derepressible 5-related acetyltransferase ofA. muciniphila, was accessible to colorectal cells by macropinocytosis and functioned as an acetyltransferase of Lys14 on histone H3 (H3K14ac). Elevated H3K14ac onHspa1aloci promoted the transcription and secretion of heat-shock protein 70 (HSP70) in cancer cells. High level of HSP70 promoted the immune activity of CTLs in vitro and in vivo. Moreover, bioengineered nanoparticles provided a safe and reliable drug delivery strategy of Amuc_2172 for CRC treatment in an allograft mice model.ConclusionAmuc_2172 reprogrammed tumour microenvironment by inducing HSP70 secretion and promoting CTL-related immune response in the process of tumourigenesis.

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