Expanding the Biosynthetic Toolbox: The Potential and Challenges of In Vitro Type II Polyketide Synthase Research

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Bibliographic Details
Title: Expanding the Biosynthetic Toolbox: The Potential and Challenges of In Vitro Type II Polyketide Synthase Research
Authors: Max A. J. Rivers, Andrew N. Lowell
Source: SynBio. 2:85-111
Publisher Information: MDPI AG, 2024.
Publication Year: 2024
Subject Terms: 0301 basic medicine, type II polyketide synthase, biocatalysis, PKS, 01 natural sciences, antibiotics, Streptomyces, 0104 chemical sciences, 03 medical and health sciences, polyketide, polyalkene, type II PKS, synthetic biology, polycyclic aromatics
Description: Type II polyketide synthase (PKS) systems are a rich source of structurally diverse polycyclic aromatic compounds with clinically relevant antibiotic and chemotherapeutic properties. The enzymes responsible for synthesizing the polyketide core, known collectively as the minimal cassette, hold potential for applications in synthetic biology. The minimal cassette provides polyketides of different chain lengths, which interact with other enzymes that are responsible for the varied cyclization patterns. Additionally, the type II PKS enzyme clusters offer a wide repertoire of tailoring enzymes for oxidations, glycosylations, cyclizations, and rearrangements. This review begins with the variety of chemical space accessible with type II PKS systems including the recently discovered highly reducing variants that produce polyalkenes instead of the archetypical polyketide motif. The main discussion analyzes the previous approaches with an emphasis on further research that is needed to characterize the minimal cassette enzymes in vitro. Finally, the potential type II PKS systems hold the potential to offer new tools in biocatalysis and synthetic biology, particularly in the production of novel antibiotics and biofuels.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 2674-0583
DOI: 10.3390/synbio2010006
Access URL: https://hdl.handle.net/10919/118465
https://doi.org/10.3390/synbio2010006
Rights: CC BY
Accession Number: edsair.doi.dedup.....ddfc5e8f6db783dfd0a1d4f7321544d5
Database: OpenAIRE
Description
Abstract:Type II polyketide synthase (PKS) systems are a rich source of structurally diverse polycyclic aromatic compounds with clinically relevant antibiotic and chemotherapeutic properties. The enzymes responsible for synthesizing the polyketide core, known collectively as the minimal cassette, hold potential for applications in synthetic biology. The minimal cassette provides polyketides of different chain lengths, which interact with other enzymes that are responsible for the varied cyclization patterns. Additionally, the type II PKS enzyme clusters offer a wide repertoire of tailoring enzymes for oxidations, glycosylations, cyclizations, and rearrangements. This review begins with the variety of chemical space accessible with type II PKS systems including the recently discovered highly reducing variants that produce polyalkenes instead of the archetypical polyketide motif. The main discussion analyzes the previous approaches with an emphasis on further research that is needed to characterize the minimal cassette enzymes in vitro. Finally, the potential type II PKS systems hold the potential to offer new tools in biocatalysis and synthetic biology, particularly in the production of novel antibiotics and biofuels.
ISSN:26740583
DOI:10.3390/synbio2010006