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Biochimie. 2018 Jan;144:9-20. doi: 10.1016/j.biochi.2017.10.003. Epub 2017 Oct 7.

Evolution of catalytic microenvironment governs substrate and product diversity in trichodiene synthase and other terpene fold enzymes.

Author information

1
School of Earth and Environmental Sciences, Central University of Himachal Pradesh, Kangra, Himachal Pradesh, 176206, India.
2
School of Life Sciences, Central University of Himachal Pradesh, Kangra, Himachal Pradesh, 176206, India. Electronic address: yusuf@daad-alumni.de.

Abstract

Trichodiene synthase, a terpene fold enzyme catalyzes the first reaction of trichodermin biosynthesis that is an economically important secondary metabolite. Sequence search analysis revealed that the proteins containing terpene fold are present in bacteria, fungi and plants. Terpene fold protein from Selaginella moellendorffii, a lycophyte, appeared at the interface of the microbes and plants in the evolutionary scale. Amino acid residues present around the catalytic pocket determines the size of the substrate as well as product molecules. It has been observed that the overall molecular evolution of the catalytic pockets dictates the choice of substrates/products of the proteins. It was further observed that N-terminus of multi-domain terpene fold proteins may assist in the interactions with the pyrophosphate part of the substrates. The phylogenetic analysis of these proteins further revealed that the enzymes are clustered into groups based on the domains present additional to the catalytic domains. We have also observed inter-domain 'puckering forceps' type motions in the multi-domains using normal mode analysis which were further correlated with their functions. The evolutionary clustering of these proteins was also influenced by the presence/absence of cofactor interacting motifs. These results may be used to modify/enhance the functions of these enzymes using protein engineering methods.

KEYWORDS:

Catalytic site evolution; Multi-domain proteins; Single domain proteins; Terpene fold; Trichodiene synthase

PMID:
29017925
DOI:
10.1016/j.biochi.2017.10.003
[Indexed for MEDLINE]

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