Elucidating and engineering thiopeptide biosynthesis

World Journal of Microbiology & Biotechnology
Philip R Bennallack, Joel S Griffitts

Abstract

Initially discovered in the mid-twentieth century, thiopeptides constitute a diverse family of bacterially produced natural products exhibiting a remarkable array of biological properties. Only in the last several years have the details of thiopeptide biosynthesis been uncovered by a combination of genomic, genetic, and biochemical approaches. Thiopeptides are now known to be ribosomally synthesized and subsequently densely modified to carry azol(in)es, dehydro amino acids, and various other pathway-specific decorations. The defining feature of thiopeptides is a central six-membered nitrogenous ring that constrains peptide macrocycles of varying sequences and sizes. Recent landmark studies have defined the precisely orchestrated posttranslational modification cascade culminating in thiopeptide product formation. Because diverse thiopeptides are processed by a relatively small number of well-conserved enzymes, it has been suggested that artificial diversification of the precursor peptide could allow a vast new chemical space to be explored for clinically important activities. The success of this strategy depends on the plasticity of thiopeptide processing machinery, an open question that warrants further investigation. There is ...Continue Reading

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Citations

Aug 8, 2018·FEMS Microbiology Reviews·Jeella Z AcedoMarco J van Belkum

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Datasets Mentioned

BETA
GE37468

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BETA
pull-down
dissection

Software Mentioned

MPAS

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