PMID- 35131263 OWN - NLM STAT- MEDLINE DCOM- 20220415 LR - 20220531 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 298 IP - 3 DP - 2022 Mar TI - RNA-dependent synthesis of ergosteryl-3beta-O-glycine in Ascomycota expands the diversity of steryl-amino acids. PG - 101657 LID - S0021-9258(22)00097-7 [pii] LID - 10.1016/j.jbc.2022.101657 [doi] LID - 101657 AB - A wide range of bacteria possess virulence factors such as aminoacyl-tRNA transferases (ATTs) that are capable of rerouting aminoacyl-transfer RNAs away from protein synthesis to conjugate amino acids onto glycerolipids. We recently showed that, although these pathways were thought to be restricted to bacteria, higher fungi also possess ergosteryl-3beta-O-L-aspartate synthases (ErdSs), which transfer the L-Asp moiety of aspartyl-tRNA(Asp) onto the 3beta-OH group of ergosterol (Erg), yielding ergosteryl-3beta-O-L-aspartate (Erg-Asp). Here, we report the discovery, in fungi, of a second type of fungal sterol-specific ATTs, namely, ergosteryl-3beta-O-glycine (Erg-Gly) synthase (ErgS). ErgS consists of a freestanding DUF2156 domain encoded by a gene distinct from and paralogous to that of ErdS. We show that the enzyme only uses Gly-tRNA(Gly) produced by an independent glycyl-tRNA synthetase (GlyRS) to transfer glycine onto the 3beta-OH of Erg, producing Erg-Gly. Phylogenomics analysis also show that the Erg-Gly synthesis pathway exists only in Ascomycota, including species of biotechnological interest, and more importantly, in human pathogens, such as Aspergillus fumigatus. The discovery of a second type of Erg-aa not only expands the repertoire of this particular class of fungal lipids but suggests that Erg-aa synthases might constitute a genuine subfamily of lipid-modifying ATTs. CI - Published by Elsevier Inc. FAU - Yakobov, Nathaniel AU - Yakobov N AD - CNRS, Genetique Moleculaire, Genomique, Microbiologie, UMR 7156, Universite de Strasbourg, Strasbourg Cedex, France. FAU - Mahmoudi, Nassira AU - Mahmoudi N AD - CNRS, Genetique Moleculaire, Genomique, Microbiologie, UMR 7156, Universite de Strasbourg, Strasbourg Cedex, France. Electronic address: nmahmoudikaidi@unistra.fr. FAU - Grob, Guillaume AU - Grob G AD - CNRS, Genetique Moleculaire, Genomique, Microbiologie, UMR 7156, Universite de Strasbourg, Strasbourg Cedex, France. FAU - Yokokawa, Daisuke AU - Yokokawa D AD - School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan. FAU - Saga, Yusuke AU - Saga Y AD - School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan. FAU - Kushiro, Tetsuo AU - Kushiro T AD - School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan. FAU - Worrell, Danielle AU - Worrell D AD - Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA. FAU - Roy, Herve AU - Roy H AD - Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA. FAU - Schaller, Hubert AU - Schaller H AD - Plant Isoprenoid Biology (PIB) Team, Institut de Biologie Moleculaire des Plantes du CNRS, Universite de Strasbourg, Strasbourg, France. FAU - Senger, Bruno AU - Senger B AD - CNRS, Genetique Moleculaire, Genomique, Microbiologie, UMR 7156, Universite de Strasbourg, Strasbourg Cedex, France. FAU - Huck, Laurence AU - Huck L AD - CNRS, Genetique Moleculaire, Genomique, Microbiologie, UMR 7156, Universite de Strasbourg, Strasbourg Cedex, France. FAU - Riera Gascon, Gisela AU - Riera Gascon G AD - CNRS, Genetique Moleculaire, Genomique, Microbiologie, UMR 7156, Universite de Strasbourg, Strasbourg Cedex, France. FAU - Becker, Hubert D AU - Becker HD AD - CNRS, Genetique Moleculaire, Genomique, Microbiologie, UMR 7156, Universite de Strasbourg, Strasbourg Cedex, France. Electronic address: h.becker@unistra.fr. FAU - Fischer, Frederic AU - Fischer F AD - CNRS, Genetique Moleculaire, Genomique, Microbiologie, UMR 7156, Universite de Strasbourg, Strasbourg Cedex, France. Electronic address: frfischer@unistra.fr. LA - eng GR - R21 AI144481/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20220204 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Amino Acids) RN - 0 (RNA, Fungal) RN - 0 (RNA, Transfer, Amino Acyl) RN - 30KYC7MIAI (Aspartic Acid) RN - TE7660XO1C (Glycine) RN - Z30RAY509F (Ergosterol) SB - IM MH - Amino Acids MH - *Ascomycota/genetics/metabolism MH - Aspartic Acid MH - *Ergosterol MH - *Glycine/biosynthesis/genetics/metabolism MH - Humans MH - RNA, Fungal/genetics/metabolism MH - RNA, Transfer, Amino Acyl/genetics/metabolism PMC - PMC8913301 OTO - NOTNLM OT - DUF2156 OT - aminoacyl-tRNA OT - ergosterol OT - ergosteryl-3beta-O-L-aspartate OT - ergosteryl-3beta-O-glycine OT - fungi OT - sterol aminoacylation COIS- Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. EDAT- 2022/02/09 06:00 MHDA- 2022/04/16 06:00 PMCR- 2022/02/04 CRDT- 2022/02/08 05:40 PHST- 2021/07/27 00:00 [received] PHST- 2022/01/13 00:00 [revised] PHST- 2022/01/16 00:00 [accepted] PHST- 2022/02/09 06:00 [pubmed] PHST- 2022/04/16 06:00 [medline] PHST- 2022/02/08 05:40 [entrez] PHST- 2022/02/04 00:00 [pmc-release] AID - S0021-9258(22)00097-7 [pii] AID - 101657 [pii] AID - 10.1016/j.jbc.2022.101657 [doi] PST - ppublish SO - J Biol Chem. 2022 Mar;298(3):101657. doi: 10.1016/j.jbc.2022.101657. Epub 2022 Feb 4.