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Biology subjects

Zhiman, S.

Publications and source records attributed to Zhiman, S..

2 recordsLinked to original sources

Deciphering the chemical landscape and potential ecological function of RiPPs from the untapped Archaea domain

Chemical communication is crucial in ecosystems with complex microbial communities. However, the difficulties inherent to the cultivation of archaea have led to a limited understanding of their chemical language, especially regarding the structure diversity and function of secondary or specialized metabolites (SMs). Our comprehensive investigation into the biosynthetic potential of archaea, combined with metabolic analyses and the first report of heterologous expression in archaea, has unveiled the previously unexplored biosynthetic capabilities and chemical diversity of archaeal ribosomally synthesized and post-translationally modified peptides (RiPPs). We have identified twenty-four new lanthipeptides of RiPPs exhibiting unique chemical characteristics, including a novel subfamily featuring an unexplored type with diamino-dicarboxylic (DADC) termini, largely expanding the chemical landscape of archaeal SMs. This sheds light on the chemical novelty of archaeal metabolites and emphasizes their potential as an untapped resource for natural product discovery. Additionally, archaeal lanthipeptides demonstrate specific antagonistic activity against haloarchaea, mediating the unique biotic interaction in the halophilic niche. Furthermore, they showcase a new ecological role of RiPPs in enhancing the hosts motility by inducing the rod-shaped cell morphology and upregulating the archaellin gene expression, facilitating the archaeal interaction with abiotic environments. These discoveries broaden our understanding of archaeal chemical language and provide promising prospects for future exploration of SM-mediated interaction. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/616454v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@3647e4org.highwire.dtl.DTLVardef@1a9ebb1org.highwire.dtl.DTLVardef@b0efdeorg.highwire.dtl.DTLVardef@53d933_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

P450-Catalyzed Biaryl Macrocyclization of Leaderless Ribosomal Peptides

Macrocyclic peptides containing biaryl motifs, predominantly derived from natural products, are valuable scaffolds due to their structural rigidity and potent bioactivity. However, current synthetic methods remain constrained by the absence of broadly applicable strategies across chemocatalytic and biocatalytic platforms. Here, we discover a versatile P450 enzyme, GpeC, capable of facilitating oxidative C-C/O/N cross-coupling for peptide biaryl macrocyclization (PBC) with leader-independent activity. Crystal structure analysis of GpeC rationalizes leader-independent property and reveals adaptive recognition that enables access to diverse biaryl-linked macrocycles. GpeC exhibits exceptional substrate promiscuity, accommodating 19 of 20 canonical amino acids and diverse noncanonical analogs within a minimal tetrapeptide scaffold. The efficient semi-synthesis of the natural product Rubrin further demonstrated the versatility of GpeC. We further introduced lytic to tetraregion (LTT), a one-step, single enzyme synthesis for modular synthesis of biaryl-cyclized tetrapeptide. Overall, GpeCs robustness and programmability position it as a broadly applicable biocatalyst for the synthesis of biaryl macrocyclic peptides.

biochemistry↗