Note: a dashed line (without arrowheads) between two compound names is meant to imply that the two names are just different instantiations of the same compound -- i.e. one may be a specific name and the other a general name, or they may both represent the same compound in different stages of a polymerization-type pathway. This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: PHB biosynthesis, polyhydroxybutyrate biosynthesis
|Superclasses:||Biosynthesis → Storage Compounds Biosynthesis|
Some taxa known to possess this pathway include : Azospirillum brasilense, Azotobacter beijerinckii, Azotobacter vinelandii, Caulobacter crescentus CB15, Cupriavidus necator, Desmonostoc muscorum, Rhodobacter sphaeroides, Streptomyces aureofaciens, Zoogloea ramigera
Polyhydroxyalkanoates (PHAs) are a class of bacterial storage compounds that accumulate inside cells in the form of inclusion bodies (granules) when carbon sources are oversupply. PHAs may accumulate to levels of up to 90% of cellular dry weight and can provide the bacterium with a source of carbon and energy during periods of nutritional deprivation. These polyesters are of industrial interest due to their biodegradability to water-soluble products, and their ability to be synthesized from renewable resources (in [Papageorgiou08] and in [Handrick01] and reviewed in [Jendrossek09]). There is evidence that archaea may also synthesize PHAs (in [Han09]).
PHAs are generally classified as short-chain-length (monomers contain 3-5 carbon atoms) (this pathway) or medium-chain-length (monomers contain 6-14 carbon atoms) (see pathway polyhydroxydecanoate biosynthesis) (in [Rehm01, Ren09]). The chain length may vary depending on organism and culture conditions. Many 3-hydroxyacids have been identified as constituents of PHA polymers and the theoretical number of copolymers is high. poly-3-hydroxybutanoate (PHB) is the most abundant storage compound in bacteria. PHB and its copolymer with 3-hydroxyvalerate have been commercialized. Considerable progress has also been made in elucidating the molecular architecture of intracellular PHA granules and identifying them as complex subcellular organelles (in [Kapetaniou05] and reviewed in [Jendrossek09]).
PHA polymerases (synthases) are the key enzymes of PHA biosynthesis. They catalyze the stereoselective, covalent linkage of a (3R)-3-hydroxyacyl-CoA thioesters in a transesterification reaction with concomitant release of coenzyme A (in [Ren09]). All PHA polymerases share a conserved active site L-cysteine residue to which the growing polymer is attached. The mechanism of PHA polymerase initiation, elongation and termination of the polymer has not yet been elucidated and no structural data are available. However, evidence suggests that these enzymes may dimerize when substrate is provided, with one subunit attached to the growing polymer chain and the other binding a new substrate molecule (reviewed in [Grage09, Jendrossek09] and in detail in [Rehm07]).
Enzymes that degrade PHAs can be of two types, those that are secreted and act extracellularly, or those that act intracellularly. They may be specific for either short-chain-length PHAs (EC 184.108.40.206) or medium-chain-length PHAs (EC 220.127.116.11) and catalyze their hydrolysis to monomeric, or oligomeric hydroxyalkanoates (see poly(3-hydroxybutyrate) depolymerase, extracellular poly(3-hydroxyoctanoate) depolymerase and intracellular poly(3-hydroxyoctanoate) depolymerase). Intracellular enzymes degrade PHAs for direct utilization, while extracellularly secreted enzymes may act on PHAs that are released from dead bacterial cells (in [Kapetaniou05] and in [Papageorgiou08]).
About This Pathway
poly-3-hydroxybutanoate (PHB), a homopolymer of (R)-3-hydroxybutanoate, is a storage material produced by a variety of bacteria in response to environmental stress. The presence of PHB in bacteria was first recognized by Lemoigne in 1926 [Lemoigne26], and has since been identified in bacteria from diverse phylogenetic groups, including proteobacteria, actinobacteria, firmicutes and cyanobacteria [Dawes73, Aneja05, Lawrence05, Ren05a, Sharma06, Calabia06, Yang06c]. The level of accumulation and the molecular weight of the PHB produced vary among bacterial species [Peoples89].
The PHB biosynthetic pathway includes only three enzymes. acetyl-CoA acetyltransferase catalyzes the reversible condensation of two acetyl-CoA molecules to acetoacetyl-CoA. Acetoacetyl-CoA is subsequently reduced to (R)-3-hydroxybutanoyl-CoA by acetoacetyl-CoA reductase, and PHB is then produced by the polymerization of (R)-3-hydroxybutanoyl-CoA via the action of poly-β-hydroxybutyrate polymerase. It is believed that the synthase enzyme remains covalently linked to the polymer chain during chain growth [Leaf98].
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