Luciferins Under Construction: A Review of Known Biosynthetic Pathways

Abstract

Bioluminescence, or the ability of a living organism to generate visible light, occurs as a result of biochemical reaction where enzyme, known as a luciferase, catalyzes the oxidation of a small-molecule substrate, known as luciferin. This advantageous trait has independently evolved dozens of times, with current estimates ranging from the most conservative 40, based on the biochemical diversity found across bioluminescence systems (Haddock et al., 2010) to 100, taking into account the physiological mechanisms involved in the behavioral control of light production across a wide range of taxa (Davis et al., 2016; Verdes and Gruber, 2017; Bessho-Uehara et al., 2020a; Lau and Oakley, 2021). Chemical structures of ten biochemically unrelated luciferins and several luciferase gene families have been described; however, a full biochemical pathway leading to light emission has been elucidated only for two: bacterial and fungal bioluminescence systems. Although the recent years have been marked by extraordinary discoveries and promising breakthroughs in understanding the molecular basis of multiple bioluminescence systems, the mechanisms of luciferin biosynthesis for many organisms remain almost entirely unknown. This article seeks to provide a succinct overview of currently known luciferins’ biosynthetic pathways.

Deazaflavin cofactor boosts earthworms Henlea bioluminescence

“…At present, there are ten unambiguously established luciferins with proven chemical structures 53 of which seven have oxidation and light emission functions located in the same molecule, two luciferins ( Diplocardia and Latia luciferins) have still unknown light-emitting species and only one (bacterial luciferin) has luciferin oxidation (aldehyde) and light emission (flavin mononucleotide FMN) functions separated between different molecules. The bacterial BL reaction follows the equation: 54 …”

Scalemic natural products

“…Bioluminescence is associated to the enzymatic production of luciferins, a class of compounds capable of light emission upon oxidation. 65 Firefly luciferin is a benzothiazole derivative [( S )-2-(6′-hydroxy-2′-benzothiazolyl)-2-thiazoline-4-carboxylic acid, ( S )-32 , d -luciferin, Scheme 4], which emits light with loss of CO 2 when oxidized by the enzyme firefly luciferase to form oxyluciferin 33 . 66…”

“…65 Moreover, d -luciferin inhibits the synthesis of l -luciferyl-CoA, and therefore self-limits its production, while an increased concentration of free l -luciferin inhibits the oxidation reaction, hindering the bioluminescence process. 65…”

“…68,69 Noteworthy, luciferase appears to show different enzymatic activity for the two enantiomers, behaving as a thioesterase towards L-luciferin (Scheme 6) and as an oxidase towards Dluciferin (Scheme 4). 65 Moreover, D-luciferin inhibits the synthesis of L-luciferyl-CoA, and therefore self-limits its production, while an increased concentration of free L-luciferin inhibits the oxidation reaction, hindering the bioluminescence process. 65 3.2 Co-expression of antipodal enzymes or directing proteins 3.2.1 Polyene cyclization.…”

Similar enzymatic functions in distinct bioluminescence systems: Evolutionary recruitment of sulfotransferases in ostracod light organs

“…Although fireflies, sea pansies, and cypridinid ostracods convergently evolved the same mechanism for luciferin sulfation, the extent of evolutionary convergence varies across levels of biological organization. These taxa convergently evolved bioluminescence as a defense mechanism -which was later co-opted for courtship in fireflies (Powell et al 2022) and ostracods (Ellis et al 2022) -but produce light by using structurally diverse organs or tissue (Peterson and Buck 1968;Spurlock and Cormier 1975;Huvard 1993), different luciferins (Tsarkova 2021), and non-homologous luciferases (Cormier and Kazuo 1964;Oba et al 2003;Oakley 2005) (Figure 1). Understanding how these taxa genetically encode luciferin sulfation and synthesizing these findings with those from other levels of biological organization -namely, organismal, organ, and tissue -will reveal the extent to which convergently evolved phenotypes may vary across levels of biological organization.…”