TY - JOUR
T1 - Enzyme evolution in natural products biosynthesis
T2 - target- or diversity-oriented?
AU - Noda-Garcia, Lianet
AU - Tawfik, Dan S.
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/12
Y1 - 2020/12
N2 - Natural product biosynthesis (NPB) is the Panda's Thumb of evolutionary biochemistry. Arm races between organisms, and ever-changing environments, result in relentless innovation. This review focusses on enzyme evolution in NPB. First, we review cases of de novo emergence, whereby a completely new enzymatic activity arose in a ligand-binding protein, or a new enzyme emerged including a completely new scaffold. Second, we briefly review the current models for enzyme evolution, and how they explain the inherent promiscuity of NPB enzymes and their tendency to produce multiple related products. We thus suggest that NPB enzymes a priori evolved to generate a specific product; they are, however, trapped in a multifunctional, generalist evolutionary state and thereby produce a diversity of products.
AB - Natural product biosynthesis (NPB) is the Panda's Thumb of evolutionary biochemistry. Arm races between organisms, and ever-changing environments, result in relentless innovation. This review focusses on enzyme evolution in NPB. First, we review cases of de novo emergence, whereby a completely new enzymatic activity arose in a ligand-binding protein, or a new enzyme emerged including a completely new scaffold. Second, we briefly review the current models for enzyme evolution, and how they explain the inherent promiscuity of NPB enzymes and their tendency to produce multiple related products. We thus suggest that NPB enzymes a priori evolved to generate a specific product; they are, however, trapped in a multifunctional, generalist evolutionary state and thereby produce a diversity of products.
KW - Chemical diversity
KW - Enzyme evolution
KW - Generalist
KW - Natural products biosynthesis
KW - Promiscuity
UR - http://www.scopus.com/inward/record.url?scp=85088930149&partnerID=8YFLogxK
U2 - 10.1016/j.cbpa.2020.05.011
DO - 10.1016/j.cbpa.2020.05.011
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C2 - 32771972
AN - SCOPUS:85088930149
SN - 1367-5931
VL - 59
SP - 147
EP - 154
JO - Current Opinion in Chemical Biology
JF - Current Opinion in Chemical Biology
ER -