Journal
CURRENT OPINION IN MICROBIOLOGY
Volume 51, Issue -, Pages 88-96Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.mib.2019.10.007
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Funding
- Biotechnology and Biological Sciences Research Council (BBSRC) [BBS/E/J/000PR9790]
- BBSRC/Innovate UK Biocatalyst Grant [BB/N02351/1]
- BBSRC [BBS/E/J/000PR9790, BB/N023536/1, BBS/E/J/000C0665, BB/M011933/1, BB/N02351X/1, BB/M017702/1] Funding Source: UKRI
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Numerous important therapeutic agents, including widely-used antibiotics, anti-cancer drugs, immunosuppressants, agrochemicals and other valuable compounds, are produced by microorganisms. Many of these are biosynthesised by modular enzymatic assembly line polyketide synthases, non ribosomal peptide synthetases, and hybrids thereof. To alter the backbone structure of these valuable but difficult to modify compounds, the respective enzymatic machineries can be engineered to create even more valuable molecules with improved properties and/or to bypass resistance mechanisms. In the past, many attempts to achieve assembly line pathway engineering failed or led to enzymes with compromised activity. Recently our understanding of assembly line structural biology, including an appreciation of the conformational changes that occur during the catalytic cycle, have improved hugely. This has proven to be a driving force for new approaches and several recent examples have demonstrated the production of new-to-nature molecules, including anti-infectives. We discuss the developments of the last few years and highlight selected, illuminating examples of assembly line engineering.
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