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Biotin (vitamin H or B7) is a coenzyme essential for all forms of life. Biotin has biological activity only when covalently attached to a few key metabolic enzyme proteins. Most organisms have only one attachment enzyme, biotin protein ligase (BPL), which attaches biotin to all target proteins. The sequences of these proteins and their substrate proteins are strongly conserved throughout biology. Structures of both the biotin ligase‐ and biotin‐acceptor domains of mammals, plants, several bacterial species, and archaea have been determined. These, together with mutational analyses of ligases and their protein substrates, illustrate the exceptional specificity of this protein modification. For example, the Escherichia coli BPL biotinylates only one of the >4000 cellular proteins. Several bifunctional bacterial biotin ligases transcriptionally regulate biotin synthesis and/or transport in concert with biotinylation. The human BPL has been demonstrated to play an important role in that mutations in the BPL encoding gene cause one form of the disease, biotin‐responsive multiple carboxylase deficiency. Promiscuous mutant versions of several BPL enzymes release biotinoyl‐AMP, the active intermediate of the ligase reaction, to solvent. The released biotinoyl‐AMP acts as a chemical biotinylation reagent that modifies lysine residues of neighboring proteins in vivo. This proximity‐dependent biotinylation (called BioID) approach has been heavily utilized in cell biology. [ABSTRACT FROM AUTHOR]

This is a review of the acyl carrier proteins (ACPs) of type II fatty acid synthesis in bacteria and mitochondria, their structures and protein interactions. Type II fatty acid synthesis in bacteria (Prog. Lipid Res. (2013) 52, 249–276; Biochim. Biophys. Acta (1996) 1302, 1–16; Annu. Rev. Biochem. (2005) 74, 791–831) and in the mitochondria of yeast and mammals (Biochim. Biophys. Acta Mol. Cell. Res. (2019) 1866, 118540; MedChemComm (2019) 10, 209–220; Elife (2016) 5, e17828; Mol. Cell (2018) 71, 567–580.e4) will be discussed only tangentially in this review. The above references are excellent recent reviews. Bacterial fatty acid synthesis has been a popular target for the development of new antimicrobials and an up-to-date review of the field has been published (Annu. Rev. Microbiol. (2022) 76, 281–304). The ACP-like proteins of secondary metabolites (e.g. polyketide synthesis will not be reviewed). Escherichia coli ACP is now called AcpP to distinguish it from the enzymes that attach (AcpS) and remove (AcpH) the 40 -phosphopantetheine (40 PP) prosthetic group. Note that the primary translation product of the acpP gene is called apoAcpP. The addition of the 40 PP prosthetic group converts apo-AcpP to holo-AcpP (commonly referred to as AcpP). Acylation of the 40 PP prosthetic group gives acyl-AcpP species. The length of the acyl chain determines the properties of the acyl-AcpP as will be discussed below. [ABSTRACT FROM AUTHOR]

Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns (1). We and others (2) are developing computation-guided strategies for [...]