BpsA (N(4)-bis(aminopropyl)spermidine synthase) is a single-module non-ribosomal peptide synthase (NRPS) (also see non-ribosomal peptide (NPR)) located in the cytoplasm[1] responsible for the process of creating branched-chain polyamines,[1] and producing spermidine and spermine.[2] It has a singular ligand in its structure involved with Fe3+ and PLIP interactions.[3] As seen by its EC number, it is a transferase (2) that transfers an alkyl or aryl group other than methyl groups (5) (2.5.1).[citation needed] BpsA was first discovered in the archaea Methanococcus jannaschii[4] and thermophile Thermococcus kodakarensis[2] and since then has been used in a variety of applications such as being used as a reporter, researching phosphopantetheinyl transferase (PPTase), and for NRPS domain recombination experiments it can be used as a model.[5] Both (hyper)thermophilic bacteria and euryarchaeotal archaea seem to conserve BpsA and orthologs as branches chains polyamines are crucial for survival.[6] There is also a second type of BpsA also known as Blue-pigment indigoidine synthetase that produces the pigment indigoidine and is found in organisms like Erwinia chrysanthemi.[7] However, not much seems to be known about this variant except that it is a synthase, and it does not yet appear to be classified under an EC number.
In thermophiles, BpsA converts N4-aminopropylspermidine to N4-bis(aminopropyl)spermidine.[2] In this pathway, aminopropyltransferase and ureohydrolase turn N1-aminopropylagmatine to agmantine and synthesize spermidine and spermine.[2] Spermine and spermadine are utilized in a variety of pathways including macromolecule production, apoptosis and proliferation equilibrium, and the induction of differentiation in cells.[8] Long Linear polyamines (such as ones found in TK-BpsA made of up spermine and spermidine) help stabilize DNA.[8] Denaturation could possible occur at high temperatures, making the stabilization crucial for organisms that thrive here. If an organism cannot stabilize its DNA, it cannot survive. TK-BpsA is a BpsA found in the archaeon Thermococcus kodakarensis and is used to study this pathway more in depth.[9] It is also a ternary complex.[10] There are a few active sites that include polyamine spermidine/spermine synthases, and loop-closures occur upon the binding of spermidine, and a catalytic center made of a Gly-Asp-Asp-Asp motif which contains reactive secondary amino group of the substrate polyamine and a sulfur atom of the product 5ʹ-methylthioadenosine with Asp 159.[9] The enzyme proves itself to be important to thermophiles as it supports growth under high-temperature conditions.[1] In this system, the C-Terminal is a flexible region of branched-chain polyamine synthase facilitates substrate specificity and catalysis.[10] This C-terminal region recognizes acceptor proteins for the enzyme and gain their flexibility from aspartate/glutamate residues.[10] The flexibility itself is promoted by a ping-pong Bi-Bi mechanism that occurs when temperatures are high.[10]
^Hidese R, Fukuda W, Niitsu M, Fujiwara S (2018). "Identification of Branched-Chain Polyamines in Hyperthermophiles". In Alcázar R, Tiburcio AG (eds.). Polyamines. Methods in Molecular Biology. Vol. 1694. New York, NY: Springer. pp. 81–94. doi:10.1007/978-1-4939-7398-9_8. ISBN978-1-4939-7398-9. PMID29080158.
