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
|Superclasses:||Biosynthesis → Other 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 [Han09a]).
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. a poly-β-hydroxybutyrate (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 18.104.22.168) or medium-chain-length PHAs (EC 22.214.171.124) 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
a poly-β-hydroxybutyrate (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, Yang06b]. 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].
Aneja05: Aneja P, Zachertowska A, Charles TC (2005). "Comparison of the symbiotic and competition phenotypes of Sinorhizobium meliloti PHB synthesis and degradation pathway mutants." Can J Microbiol 51(7);599-604. PMID: 16175209
Grage09: Grage K, Jahns AC, Parlane N, Palanisamy R, Rasiah IA, Atwood JA, Rehm BH (2009). "Bacterial polyhydroxyalkanoate granules: biogenesis, structure, and potential use as nano-/micro-beads in biotechnological and biomedical applications." Biomacromolecules 10(4);660-9. PMID: 19275166
Han09a: Han J, Lu Q, Zhou L, Liu H, Xiang H (2009). "Identification of the polyhydroxyalkanoate (PHA)-specific acetoacetyl coenzyme A reductase among multiple FabG paralogs in Haloarcula hispanica and reconstruction of the PHA biosynthetic pathway in Haloferax volcanii." Appl Environ Microbiol 75(19);6168-75. PMID: 19648370
Handrick01: Handrick R, Reinhardt S, Focarete ML, Scandola M, Adamus G, Kowalczuk M, Jendrossek D (2001). "A new type of thermoalkalophilic hydrolase of Paucimonas lemoignei with high specificity for amorphous polyesters of short chain-length hydroxyalkanoic acids." J Biol Chem 276(39);36215-24. PMID: 11457823
Jia01: Jia Y, Yuan W, Wodzinska J, Park C, Sinskey AJ, Stubbe J (2001). "Mechanistic studies on class I polyhydroxybutyrate (PHB) synthase from Ralstonia eutropha: class I and III synthases share a similar catalytic mechanism." Biochemistry 40(4);1011-9. PMID: 11170423
Kapetaniou05: Kapetaniou EG, Braaz R, Jendrossek D, Papageorgiou AC (2005). "Crystallization and preliminary X-ray analysis of a novel thermoalkalophilic poly(3-hydroxybutyrate) depolymerase (PhaZ7) from Paucimonas lemoignei." Acta Crystallogr Sect F Struct Biol Cryst Commun 61(Pt 5);479-81. PMID: 16511073
Lawrence05: Lawrence AG, Choi J, Rha C, Stubbe J, Sinskey AJ (2005). "In vitro analysis of the chain termination reaction in the synthesis of poly-(R)-beta-hydroxybutyrate by the class III synthase from Allochromatium vinosum." Biomacromolecules 6(4);2113-9. PMID: 16004452
Papageorgiou08: Papageorgiou AC, Hermawan S, Singh CB, Jendrossek D (2008). "Structural basis of poly(3-hydroxybutyrate) hydrolysis by PhaZ7 depolymerase from Paucimonas lemoignei." J Mol Biol 382(5);1184-94. PMID: 18706425
Peoples89: Peoples OP, Sinskey AJ (1989). "Poly-beta-hydroxybutyrate (PHB) biosynthesis in Alcaligenes eutrophus H16. Identification and characterization of the PHB polymerase gene (phbC)." J Biol Chem 264(26);15298-303. PMID: 2670936
Rehm01: Rehm BH, Mitsky TA, Steinbuchel A (2001). "Role of fatty acid de novo biosynthesis in polyhydroxyalkanoic acid (PHA) and rhamnolipid synthesis by pseudomonads: establishment of the transacylase (PhaG)-mediated pathway for PHA biosynthesis in Escherichia coli." Appl Environ Microbiol 67(7);3102-9. PMID: 11425728
Ren05a: Ren Q, van Beilen JB, Sierro N, Zinn M, Kessler B, Witholt B (2005). "Expression of PHA polymerase genes of Pseudomonas putida in Escherichia coli and its effect on PHA formation." Antonie Van Leeuwenhoek 87(2);91-100. PMID: 15793618
Ren09: Ren Q, de Roo G, Witholt B, Zinn M, Thony-Meyer L (2009). "Overexpression and characterization of medium-chain-length polyhydroxyalkanoate granule bound polymerases from Pseudomonas putida GPo1." Microb Cell Fact 8;60. PMID: 19925642
Yang06b: Yang MK, Lin YC, Shen CH (2006). "Identification of two gene loci involved in poly-beta-hydroxybutyrate production in Rhodobacter sphaeroides FJ1." J Microbiol Immunol Infect 39(1);18-27. PMID: 16440119
Alber06: Alber BE, Spanheimer R, Ebenau-Jehle C, Fuchs G (2006). "Study of an alternate glyoxylate cycle for acetate assimilation by Rhodobacter sphaeroides." Mol Microbiol 61(2);297-309. PMID: 16856937
Colby92: Colby GD, Chen JS (1992). "Purification and properties of 3-hydroxybutyryl-coenzyme A dehydrogenase from Clostridium beijerinckii ("Clostridium butylicum") NRRL B593." Appl Environ Microbiol 58(10);3297-302. PMID: 1444364
Dekishima11: Dekishima Y, Lan EI, Shen CR, Cho KM, Liao JC (2011). "Extending Carbon Chain Length of 1-Butanol Pathway for 1-Hexanol Synthesis from Glucose by Engineered Escherichia coli." J Am Chem Soc 133(30);11399-401. PMID: 21707101
Gerngross94: Gerngross TU, Snell KD, Peoples OP, Sinskey AJ, Csuhai E, Masamune S, Stubbe J (1994). "Overexpression and purification of the soluble polyhydroxyalkanoate synthase from Alcaligenes eutrophus: evidence for a required posttranslational modification for catalytic activity." Biochemistry 33(31);9311-20. PMID: 8049232
Haapalainen07: Haapalainen AM, Merilainen G, Pirila PL, Kondo N, Fukao T, Wierenga RK (2007). "Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function." Biochemistry 46(14);4305-21. PMID: 17371050
Hartmanis82: Hartmanis MG, Stadtman TC (1982). "Isolation of a selenium-containing thiolase from Clostridium kluyveri: identification of the selenium moiety as selenomethionine." Proc Natl Acad Sci U S A 79(16);4912-6. PMID: 6956900
Hawkins14: Hawkins AB, Adams MW, Kelly RM (2014). "Conversion of 4-Hydroxybutyrate to Acetyl-CoA and its Anapleurosis in the Metallosphaera sedula 3-Hydroxypropionate/4-Hydroxybutyrate Carbon Fixation Pathway." Appl Environ Microbiol. PMID: 24532060
Haywood88: Haywood G.W., Anderson A.J., Chu L., Dawes E.A. (1988). "The role of NADH- and NADPH-linked acetoacetyl-CoA reductases in the poly-3-hydroxybutyrate synthesizing organism Alcaligenes eutrophus." FEMS Microbiology Letters 52(3):259-264.
Hedl02: Hedl M, Sutherlin A, Wilding EI, Mazzulla M, McDevitt D, Lane P, Burgner JW, Lehnbeuter KR, Stauffacher CV, Gwynn MN, Rodwell VW (2002). "Enterococcus faecalis acetoacetyl-coenzyme A thiolase/3-hydroxy-3-methylglutaryl-coenzyme A reductase, a dual-function protein of isopentenyl diphosphate biosynthesis." J Bacteriol 184(8);2116-22. PMID: 11914342
Jin12: Jin H, Song Z, Nikolau BJ (2012). "Reverse Genetic Characterization of two Paralogous Acetoacetyl-CoA Thiolase genes in Arabidopsis Reveals Their Importance in Plant Growth and Development." Plant J. PMID: 22332816
Kursula05: Kursula P, Sikkila H, Fukao T, Kondo N, Wierenga RK (2005). "High resolution crystal structures of human cytosolic thiolase (CT): a comparison of the active sites of human CT, bacterial thiolase, and bacterial KAS I." J Mol Biol 347(1);189-201. PMID: 15733928
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