Skip to main content
Log in

Unusual Evolution of Cephalopod Tryptophan Indole-Lyases

Journal of Molecular Evolution Aims and scope Submit manuscript


Tryptophan indole-lyase (TIL), a pyridoxal-5-phosphate-dependent enzyme, catalyzes the hydrolysis of l-tryptophan (l-Trp) to indole and ammonium pyruvate. TIL is widely distributed among bacteria and bacterial TILs consist of a D2-symmetric homotetramer. On the other hand, TIL genes are also present in several metazoans. Cephalopods have two TILs, TILα and TILβ, which are believed to be derived from a gene duplication that occurred before octopus and squid diverged. However, both TILα and TILβ individually contain disruptive amino acid substitutions for TIL activity, and neither was active when expressed alone. When TILα and TILβ were coexpressed, however, they formed a heterotetramer that exhibited low TIL activity. The loss of TIL activity of the heterotetramer following site-directed mutagenesis strongly suggests that the active heterotetramer contains the TILα/TILβ heterodimer. Metazoan TILs generally have lower kcat values for l-Trp than those of bacterial TILs, but such low TIL activity may be rather suitable for metazoan physiology, where l-Trp is in high demand. Therefore, reduced activity may have been a less likely target for purifying selection in the evolution of cephalopod TILs. Meanwhile, the unusual evolution of cephalopod TILs may indicate the difficulty of post-gene duplication evolution of enzymes with catalytic sites contributed by multiple subunits, such as TIL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Hajime Julie Yuasa.

Ethics declarations

Conflict of interest

The author declares no conflict of interest.

Additional information

Handling editor: John Bracht.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 214 KB)

Supplementary file2 (XLSX 19 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yuasa, H.J. Unusual Evolution of Cephalopod Tryptophan Indole-Lyases. J Mol Evol 91, 912–921 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: