Enzymatic promiscuity and the evolution of bioluminescence

Abstract

Bioluminescence occurs when an enzyme, known as a luciferase, oxidizes a small‐molecule substrate, known as a luciferin. Nature has evolved multiple distinct luciferases and luciferins independently, all of which accomplish the impressive feat of light emission. One of the best‐known examples of bioluminescence is exhibited by fireflies, a class of beetles that use d‐luciferin as their substrate. The evolution of bioluminescence in beetles is thought to have emerged from ancestral fatty acyl‐CoA synthetase (ACS) enzymes present in all insects. This theory is supported by multiple lines of evidence: Beetle luciferases share high sequence identity with these enzymes, often retain ACS activity, and some ACS enzymes from nonluminous insects can catalyze bioluminescence from synthetic d‐luciferin analogues. Recent sequencing of firefly genomes and transcriptomes further illuminates how the duplication of ACS enzymes and subsequent diversification drove the evolution of bioluminescence. These genetic analyses have also uncovered candidate enzymes that may participate in luciferin metabolism. With the publication of the genomes and transcriptomes of fireflies and related insects, we are now better positioned to dissect and learn from the evolution of bioluminescence in beetles.

Enzyme promiscuity and evolution in light of cellular metabolism

“…Coincidental, promiscuous activities serve as a starting point and, via mutation and selection, these gradually become the native, physiological function of the new enzyme. Stephen Miller and Spencer Adams [2] describe a specific case of duplication and divergence of a fatty acyl‐CoA synthetase that led to insect luciferases that were repurposed to generate light by oxidizing luciferin. Margaret Glasner and co‐authors [3] address another main source of new enzymes – horizontal gene transfer – and how, in combination with promiscuity, this enables the evolution of new metabolic pathways.…”

Luminescence of Cypridina Luciferin in the Presence of Human Plasma Alpha 1-Acid Glycoprotein

“…When we considered hAGP as a luciferase to be used for a reporter assay or in vivo imaging, the luminescence intensity from the combination of hAGP with Cypridina luciferin was much lower than that from known luciferin-luciferase systems ( Table 1 ). However, because molecular evolutionary studies have reported better bioluminescence systems using a non-natural luciferase or a synthetic luciferin analog [ 41 , 42 , 43 ], molecular engineering of hAGP or synthetic improvement of Cypridina luciferin could produce a practical Cypridina luciferin-based hAGP detection system to observe biological processes. Possibly, since known luciferases do not originate from mammalian proteins, the hAGP-based system could allow us to observe an intact biological event in mammalian systems.…”

Resurrecting the ancient glow of the fireflies

“…Acyl-CoA synthetic activities of ancestral firefly luciferases Firefly luciferases are bifunctional enzymes; in addition to luciferase (luminescence) activity, they have a "promiscuous" acyl-CoA synthetic (ACS) activity to various fatty acids ( Fig. 1A) (13)(14)(15). Consequently, it has been hypothesized that the firefly luciferases originated from a fatty acyl-CoA synthetase (15).…”

“…1A) (13)(14)(15). Consequently, it has been hypothesized that the firefly luciferases originated from a fatty acyl-CoA synthetase (15). We examined ACS activities of the seven ancestral luciferases using lauric acid as a substrate.…”