Polyketide β-branching: diversity, mechanism and selectivity
P D Walker1, A N M Weir2, C L Willis2
1Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Natural Product Reports
|October 15, 2020
Summary
Polyketide biosynthesis involves polyketide synthases (PKSs) and 3-hydroxy-3-methylglutaryl synthase (HMGS) for β-branching. This review details β-branch incorporation mechanisms and their role in biologically active natural products.
Area of Science:
- Biochemistry
- Natural Product Chemistry
- Synthetic Biology
Background:
- Polyketides are diverse natural products with pharmaceutical and agrochemical applications.
- Polyketide biosynthesis is regulated by polyketide synthases (PKSs).
- β-branching is a key modification in polyketide structures, influencing biological activity.
Purpose of the Study:
- To review the diversity of β-branch incorporation in polyketides from 2008 to August 2020.
- To elucidate the mechanistic details of catalytic steps involved in β-branching.
- To discuss the role of β-branches in polyketide function and PKS selectivity.
Main Methods:
- Literature review of studies on polyketide biosynthesis and β-branching.
- Analysis of mechanistic details of 3-hydroxy-3-methylglutaryl synthase (HMGS) activity.
- Examination of PKS selectivity in β-branch incorporation.
Main Results:
- Detailed summary of β-branch diversity and incorporation mechanisms.
- Elucidation of the role of HMGS in catalyzing aldol addition, dehydration, and decarboxylation.
- Discussion of polyketides with multiple β-branches and PKS fidelity.
Conclusions:
- β-branching significantly diversifies polyketide structures and biological activities.
- HMGS plays a crucial role in generating β-alkyl branches via specific catalytic steps.
- Understanding β-branching mechanisms aids in data mining and the development of novel biologically active compounds.
Related Concept Videos
01:17Radical Chain-Growth Polymerization: Chain Branching
2.3K
The skeletal structure of polymers synthesized via radical polymerization is always branched. For example, the polymerization of ethylene by radical polymerization results in a low-density grade of polyethylene with a heavily branched skeletal structure. Here, the radical site abstracts hydrogen from the growing chain, and the radical site shifts from the end (a primary carbon center) to anywhere within the growing chain (a secondary carbon center). Consequently, the part of the chain from the...
2.3K
01:14Polymer Classification: Architecture
3.5K
Polymers are classified as linear or branched on the basis of their chain architecture. The polymer chains in linear polymers have a long chain-like structure with minimal to no branching at all. Even if a polymer features large substituent groups on the monomer, which appear as branches to the skeleton, it is not considered a branched polymer. A branched polymer contains secondary polymer chains that arise from the main polymer chain. The branching occurs when the polymer growth shifts from...
3.5K
01:29Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
5.2K
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.
5.2K
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
15.8K
If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
15.8K
02:35Regioselectivity of Electrophilic Additions-Peroxide Effect
9.9K
In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov’s rule. For example, the addition of hydrogen bromide to 2-methylpropene in the presence of peroxides gives 1-bromo-2-methylpropane. This addition reaction proceeds via a free radical mechanism, which reverses the regioselectivity. The free radical reaction mechanism involves three stages: initiation, propagation, and termination.
9.9K
01:09Radical Chain-Growth Polymerization: Mechanism
3.2K
The radical chain-growth polymerization mechanism consists of three steps: initiation, propagation, and termination of polymerization. The polymerization initiates when a free radical generated from the radical initiator adds to the unsaturated bond in the monomer. The unpaired electron of the free radical and one π electron in the unsaturated bond creates a σ bond between the free radical and the monomer. As a result, the other π electron in the unsaturated bond converts this species into...
3.2K