Probing the structure and function of acyl carrier proteins to unlock the strategic redesign of type II polyketide biosynthetic pathways

Type II polyketide synthases (PKSs) are protein assemblies, encoded by biosynthetic gene clusters in microorganisms, that manufacture structurally complex and pharmacologically relevant molecules. Acyl carrier proteins (ACPs) play a central role in biosynthesis by shuttling malonyl-based building bl...

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Published inThe Journal of biological chemistry Vol. 296; p. 100328
Main Authors Sulpizio, Ariana, Crawford, Callie E.W., Koweek, Rebecca S., Charkoudian, Louise K.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.01.2021
American Society for Biochemistry and Molecular Biology
Subjects
acyl carrier protein (ACP)
biosynthesis
fatty acid
JBC Reviews
polyketide
protein crosslinking
AntF
acyl carrier protein (ACP)
A
AntD
FT-ICR-MS
DH
fatty acid
HR
DEBS
PPTase
protein crosslinking
Oxy
KSCLF
biosynthesis
FabA
Ppant
FabF
BGC
Iga
NRPS
polyketide
KR
KS
ACP
CoA
Iga10
Iga11
FAS
PKS
CLF
PCP
AcpP
Acyl carrier protein (ACP)
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Summary:Type II polyketide synthases (PKSs) are protein assemblies, encoded by biosynthetic gene clusters in microorganisms, that manufacture structurally complex and pharmacologically relevant molecules. Acyl carrier proteins (ACPs) play a central role in biosynthesis by shuttling malonyl-based building blocks and polyketide intermediates to catalytic partners for chemical transformations. Because ACPs serve as central hubs in type II PKSs, they can also represent roadblocks to successfully engineering synthases capable of manufacturing ‘unnatural natural products.’ Therefore, understanding ACP conformational dynamics and protein interactions is essential to enable the strategic redesign of type II PKSs. However, the inherent flexibility and transience of ACP interactions pose challenges to gaining insight into ACP structure and function. In this review, we summarize how the application of chemical probes and molecular dynamic simulations has increased our understanding of the structure and function of type II PKS ACPs. We also share how integrating these advances in type II PKS ACP research with newfound access to key enzyme partners, such as the ketosynthase-chain length factor, sets the stage to unlock new biosynthetic potential.
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These authors contributed equally.
ISSN:0021-9258
1083-351X
DOI:10.1016/j.jbc.2021.100328