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The development of mild, efficient, and enantioselective methods for preparing chiral building blocks from simple, renewable carbon units has been a long‐term goal of the sustainable chemical industry. Mandelate derivatives are valuable pharmaceutical intermediates and chiral resolving agents, but their manufacture relies heavily on highly toxic cyanide. Herein, we report (S)‐4‐hydroxymandelate synthase (HmaS)‐centered biocatalytic cascades for the synthesis of mandelates from benzaldehydes and glycine. We show that HmaS can be engineered to perform R‐selective hydroxylation by single‐point mutation, empowering the stereodivergent synthesis of both (S)‐ and (R)‐mandelate derivatives. These biocatalytic cascades enabled the production of various mandelate derivatives with high atom economy as well as excellent yields (up to 98 %) and ee values (up to >99 %). This methodology offers an effective cyanide‐free technology for greener and sustainable production of mandelate derivatives. [ABSTRACT FROM AUTHOR]

The development of mild, efficient, and enantioselective methods for preparing chiral building blocks from simple, renewable carbon units has been a long‐term goal of the sustainable chemical industry. Mandelate derivatives are valuable pharmaceutical intermediates and chiral resolving agents, but their manufacture relies heavily on highly toxic cyanide. Herein, we report (S)‐4‐hydroxymandelate synthase (HmaS)‐centered biocatalytic cascades for the synthesis of mandelates from benzaldehydes and glycine. We show that HmaS can be engineered to perform R‐selective hydroxylation by single‐point mutation, empowering the stereodivergent synthesis of both (S)‐ and (R)‐mandelate derivatives. These biocatalytic cascades enabled the production of various mandelate derivatives with high atom economy as well as excellent yields (up to 98 %) and ee values (up to >99 %). This methodology offers an effective cyanide‐free technology for greener and sustainable production of mandelate derivatives. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is a common epitranscriptional mRNA modification in eukaryotes. Thirteen putative m6A readers, mostly annotated as EVOLUTIONARILY CONSERVED C-TERMINAL REGION (ECT) proteins, have been identified in Arabidopsis (Arabidopsis thaliana), but few have been characterized. Here, we show that the Arabidopsis m6A reader ECT1 modulates salicylic acid (SA)–mediated plant stress responses. ECT1 undergoes liquid–liquid phase separation in vitro, and its N-terminal prion-like domain is critical for forming in vivo cytosolic biomolecular condensates in response to SA or bacterial pathogens. Fluorescence-activated particle sorting coupled with quantitative PCR analyses unveiled that ECT1 sequesters SA-induced m6A modification-prone mRNAs through its conserved aromatic cage to facilitate their decay in cytosolic condensates, thereby dampening SA-mediated stress responses. Consistent with this finding, ECT1 overexpression promotes bacterial multiplication in plants. Collectively, our findings unequivocally link ECT1-associated cytosolic condensates to SA-dependent plant stress responses, advancing the current understanding of m6A readers and the SA signaling network. The m6A reader EVOLUTIONARILY CONSERVED C-TERMINAL REGION 1 modulates salicylic acid–dependent plant stress responses, such as growth inhibition and cell death, in cytosolic biomolecular condensates. [ABSTRACT FROM AUTHOR]

The plant stress hormone salicylic acid (SA) participates in local and systemic acquired resistance, which eventually leads to whole-plant resistance to bacterial pathogens. However, if SA-mediated signaling is not appropriately controlled, plants incur defense-associated fitness costs such as growth inhibition and cell death. Despite its importance, to date only a few components counteracting the SA-primed stress responses have been identified in Arabidopsis (Arabidopsis thaliana). These include other plant hormones such as jasmonic acid and abscisic acid, and proteins such as LESION SIMULATING DISEASE1, a transcription coregulator. Here, we describe PLANT NATRIURETIC PEPTIDE A (PNP-A), a functional analog to vertebrate atrial natriuretic peptides, that appears to antagonize the SA-mediated plant stress responses. While loss of PNP-A potentiates SA-mediated signaling, exogenous application of synthetic PNP-A or overexpression of PNP-A significantly compromises the SA-primed immune responses. Moreover, we identify a plasma membrane–localized receptor-like protein, PNP-R2, that interacts with PNP-A and is required to initiate the PNP-A–mediated intracellular signaling. In summary, our work identifies a peptide and its putative cognate receptor as counteracting both SA-mediated signaling and SA-primed cell death in Arabidopsis. [ABSTRACT FROM AUTHOR]