Promiscuous Enzyme Activity as a Driver of Allo and Iso Convergent Evolution, Lessons from the β-lactamases

Abstract

The probability of the evolution of a character depends on two factors: the probability of moving from one character state to another character state and the probability of the new character state fixation. More the evolution of a character is probable more convergent evolution will be witnessed, consequently, convergent evolution could mean that the convergent character evolution result as a combination of these two factors. We investigate this phenomenon by studying the convergent evolution of biochemical functions. We use for the investigation the case of β-lactamases. β-lactamases hydrolyzes β-lactams which are antimicrobials able to block the DD-peptidases involved in bacterial cell wall synthesis. β-lactamase activity is present in two different superfamilies: the metallo-β-lactamase and the serine β-lactamase superfamily. The mechanism used to hydrolyze the β-lactam is different for the two superfamilies. We named this kind of evolution an allo-convergent evolution. We further show that the β-lactamase activity evolved several times within each superfamily, a convergent evolution type that we named iso-convergent evolution. Both types of convergent evolution can be explained by the two evolutionary mechanisms discussed above. The probability of moving from one state to another is explaining the promiscuous β-lactamase activity present in the ancestral sequences of each superfamily, while the probability of fixation is explained in part, by positive selection as the organisms having β-lactamase activity allows them to resist to organism secreting β-lactams. Indeed a mutation increasing the β-lactamases activity will be selected as the organisms having this activity will have an advantage over the others.

Could β-Lactam Antibiotics Block Humoral Immunity?

“…Thus a landscape of cross enzymatic activities among MBLs enzyme superfamily was reported ( 31 , 77 , 80 – 83 ). Therefore, MBLs’ cross enzymatic activities (hydrolase and nuclease) among different domains of the living were identified, whereas different enzymatic activities observed may be related to divergent host substrates ( 17 ). The interspecies common enzymatic activities can be explained by the highly conserved MBLs catalytic site ( Figure 4 ) ( 81 , 84 , 85 ).…”

“…First of all, it works by inhibiting the bacterial peptidoglycan cell wall synthesis ( 16 ). β-lactamases enzymes hydrolyse the β-lactam antibiotics and may also have different nuclease and hydrolases activities ( 17 – 24 ). Two mechanistically distincts superfamilies of β-lactamases with two distincts ancestors are described, the nucleophilic serine β-lactamases (class A/C/D); and the zinc ion dependent metallo-β-lactamases (class B) ( 17 , 25 – 27 ).…”

“…β-lactamases enzymes hydrolyse the β-lactam antibiotics and may also have different nuclease and hydrolases activities ( 17 – 24 ). Two mechanistically distincts superfamilies of β-lactamases with two distincts ancestors are described, the nucleophilic serine β-lactamases (class A/C/D); and the zinc ion dependent metallo-β-lactamases (class B) ( 17 , 25 – 27 ). In human, 18 metallo-β-lactamases (hMBLs) enzymes have been identified ( Table 1 ) ( 28 ).…”

A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin

“…Previously reported in the literature, MBL fold proteins can exhibit different promiscuous enzymatic activities such as nuclease and/or ribonuclease activity 14 , 15 . Here, in addition to the detected β-lactam-hydrolysing and ascorbic acid degradation activities of this enzyme, its nuclease and ribonuclease activities were investigated.…”

Dual RNase and β-lactamase Activity of a Single Enzyme Encoded in Archaea

“…Finally, the existence of enzymes in the world of archaea with multiple activities such as β-lactamase, ribonuclease, and glyoxalase II shows that β-lactamase enzymes are not only a defense system against β-lactam antibiotics. These multiple activities appear as promiscuous activities of these MBL fold enzymes, as suggested in the literature through sequence similarity network analysis [ 25 , 27 ]. Moreover, very recently, RNA-hydrolysis activity of bacterial class B metallo-β-lactamase IMP-1 has been reported experimentally [ 28 ].…”