Four billion years of microbial terpenome evolution

Abstract

Terpenoids, also known as isoprenoids, are the largest and most diverse class of organic compounds in nature and are involved in many membrane-associated cellular processes, including membrane organization, electron transport chain, cell signaling, and phototrophy. Terpenoids are ancient compounds with their origin presumably before the last universal common ancestor. However, Bacteria and Archaea are known to possess two distinct terpenoid repertoires and utilize terpenoids differently. Most notably, Archaea constitute their cellular membrane solely made of terpenoid-based phospholipids, contrary to the bacterial membrane that consists of fatty acid-based phospholipids. Thus, the composition of ancestral membranes at the beginning of cellular life and the diversification of terpenoids in early life remain enigmatic. This review addresses these key issues through comprehensive phylogenomic analyses of extant terpenoid biosynthesis enzymes in Bacteria and Archaea. We aim to infer the basal components of terpenoid biosynthesis machinery that have an ancient origin before the divergence of the two domains and shed light on the deep evolutionary connection between terpenoid biochemistry and early life.

Regulatory and Sensing Iron-Sulfur Clusters: New Insights and Unanswered Questions

“…Archaea are an ancient form of prokaryotic life that is estimated to have diverged over 3.9 billion years ago [201][202][203]. The archaeal iron-sulfur biogenesis pathway is not highly conserved between archaea species or between archaea, bacteria, and eukaryotes [204].…”

Unraveling the multiplicity of geranylgeranyl reductases in Archaea: potential roles in saturation of terpenoids

“…The enzymes responsible for chain elongation and modification of membrane-associated terpenoids in archaea remain unknown. Based on the canonical pathways in bacteria, this likely occurs through cis -isoprenyl diphosphate synthase (IPPS) or trans -IPPS enzymes which catalyze the head-to-tail condensation of isoprene units (Hoshino and Villanueva 2023 ). Specifically, the synthesis of squalene and carotenoids in archaea could be catalyzed by homologs of enzymes, such as phytoene synthase (CrtB) or squalene synthase (SQS) (Hoshino and Villanueva 2023 ).…”

Genome Mining Reveals a UbiA-Type Prenyltransferase Access to Farnesylation of Diketopiperazines

“…Widely distributed in nature, meroterpenoids are a class of terpenoid-containing hybrid natural products, which have gathered attention in the past decades due to their remarkable pharmacological activities and diversified biosynthetic logic. − According to their biosynthetic origin, meroterpenoids consist of the terpenoid fragment and non-terpenoid fragment , and are classified as polyketide-terpenoids (e.g., pyripyropene A and mycophenolic acid), , shikimate-terpenoids (e.g., mangnardones A and tricycloalternarene A), , and indole-terpenoids (e.g., sespendole, paxilline, griseocazines, and drimentines) (Figure ). − To date, a large number of meroterpenoids in nature have been isolated, purified, and fully characterized, with some of their biosynthetic pathways clearly elucidated. ,,, Generally, the critical prenylation reactions are catalyzed by prenyltransferases (PTases), which attach isopentenyl groups of different lengths (e.g., DMAPP, GPP, FPP, GGPP) onto varied acceptors via the Friedel–Crafts alkylation reaction mechanism. − …”

“…Based on their characteristics, PTases are classified into ABBA-type soluble aromatic PTases, isoprenoid synthase-type soluble PTases, and UbiA-type membrane-bound PTases. ,, These three classes of enzymes are quite distinct in their reaction scopes. PTases of the ABBA family primarily catalyze the transfer of DMAPP (C5 unit) onto indole derivatives, including simple tryptophan and diketopiperazines (DKPs) containing a tryptophan. − Isoprenoid synthase-type soluble PTases are widely distributed in the biosynthesis of indole diterpenoids by catalyzing the geranylgeranylation of indole-3-glycerol phosphate with GGPP (C20 unit) as the prenyl donor. ,, There are a few exceptions, such as DmtC1 and GczC derived from actinomycetes, which belong to the isoprenoid synthase family of PTase and catalyze the farnesylation of indole DKPs in the biosynthesis of drimentines and griseocazines (C15 unit). , Besides, a unique chimeric PTase SpdE, comprising an isoprenoid synthase domain and a dimethylallyltryptophan synthase (DMATS) domain, is responsible for the biosynthesis of a rare indole sesquiterpene, sespendole, in fungi .…”

“…14−17 Based on their characteristics, PTases are classified into ABBA-type soluble aromatic PTases, isoprenoid synthase-type soluble PTases, and UbiA-type membrane-bound PTases. 2,18,19 These three classes of enzymes are quite distinct in their reaction scopes. PTases of the ABBA family primarily catalyze the transfer of DMAPP (C5 unit) onto indole derivatives, including simple tryptophan and diketopiperazines (DKPs) containing a tryptophan.…”