Methylotroph

Methylotrophs are a diverse group of microorganisms that can use reduced one-carbon compounds, such as methanol or methane, as the carbon source for their growth; and multi-carbon compounds that contain no carbon-carbon bonds, such as dimethyl ether and dimethylamine. This group of microorganisms also includes those capable of assimilating reduced one-carbon compounds by way of carbon dioxide using the ribulose bisphosphate pathway. These organisms should not be confused with methanogens which on the contrary produce methane as a by-product from various one-carbon compounds such as carbon dioxide.Some methylotrophs can degrade the greenhouse gas methane, and in this case they are called methanotrophs. The methanotroph Methylococcus capsulatus is used to degrade methane and other substrates. The abundance, purity, and low price of methanol compared to commonly used sugars make methylotrophs competent organisms for production of amino acids, vitamins, recombinant proteins, single-cell proteins, co-enzymes and cytochromes. Methylotrophs are a diverse group of microorganisms that can use reduced one-carbon compounds, such as methanol or methane, as the carbon source for their growth; and multi-carbon compounds that contain no carbon-carbon bonds, such as dimethyl ether and dimethylamine. This group of microorganisms also includes those capable of assimilating reduced one-carbon compounds by way of carbon dioxide using the ribulose bisphosphate pathway. These organisms should not be confused with methanogens which on the contrary produce methane as a by-product from various one-carbon compounds such as carbon dioxide.Some methylotrophs can degrade the greenhouse gas methane, and in this case they are called methanotrophs. The methanotroph Methylococcus capsulatus is used to degrade methane and other substrates. The abundance, purity, and low price of methanol compared to commonly used sugars make methylotrophs competent organisms for production of amino acids, vitamins, recombinant proteins, single-cell proteins, co-enzymes and cytochromes. The key intermediate in methylotrophic metabolism is formaldehyde, which can be diverted to either assimilatory or dissimilatory pathways. Methylotrophs produce formaldehyde through oxidation of methanol and/or methane. Methane oxidation requires the enzyme methane monooxygenase (MMO). Methylotrophs with this enzyme are given the name methanotrophs. The oxidation of methane (or methanol) can be assimilatory or dissimilatory in nature (See Figure 1). If dissimilatory, the formaldehyde intermediate is oxidized completely into CO 2 {displaystyle {ce {CO2}}} to produce reductant and energy. If assimilatory, the formaldehyde intermediate is used to synthesize a 3-Carbon ( C 3 {displaystyle {{ce {C3}}}} ) compound for the production of biomass. Many methylotrophs use multi-carbon compounds for anabolism, thus limiting their use of formaldehyde to dissimilatory processes, however methanotrophs are generally limited to only C 1 { extstyle {{ce {C1}}}} metabolism. Methylotrophs use the electron transport chain to conserve energy produced from the oxidation of C 1 {displaystyle {{ce {C1}}}} compounds. An additional activation step is required in methanotrophic metabolism to allow degradation of chemically-stable methane. This oxidation to methanol is catalyzed by MMO, which incorporates one oxygen atom from O 2 {displaystyle {ce {O2}}} into methane and reduces the other oxygen atom to water, requiring two equivalents of reducing power. Methanol is then oxidized to formaldehyde through the action of methanol dehydrogenase (MDH) in bacteria, or a non-specific alcohol oxidase in yeast. Electrons from methanol oxidation are passed to a membrane-associated quinone of the electron transport chain to produce ATP {displaystyle {{ce {ATP}}}} . In dissimilatory processes, formaldehyde is completely oxidized to CO 2 {displaystyle {ce {CO2}}} and excreted. Formaldehyde is oxidized to formate via the action of Formaldehyde dehydrogenase (FALDH), which provides electrons directly to a membrane associated quinone of the electron transport chain, usually cytochrome b or c. In the case of NAD + {displaystyle {{ce {NAD+}}}} associated dehydrogenases, NADH {displaystyle {{ce {NADH}}}} is produced. Finally, formate is oxidized to CO 2 {displaystyle {ce {CO2}}} by cytoplasmic or membrane-bound Formate dehydrogenase (FDH), producing NADH {displaystyle {{ce {NADH}}}} and CO 2 {displaystyle {ce {CO2}}} . The main metabolic challenge for methylotrophs is the assimilation of single carbon units into biomass. Through de novo synthesis, Methylotrophs must form carbon-carbon bonds between 1-Carbon ( C 1 {displaystyle {{ce {C1}}}} ) molecules. This is an energy intensive process, which facultative methylotrophs avoid by using a range of larger organic compounds. However, obligate methylotrophs must assimilate C 1 {displaystyle {{ce {C1}}}} molecules. There are four distinct assimilation pathways with the common theme of generating one C 3 {displaystyle {{ce {C3}}}} molecule. Bacteria use three of these pathways while Fungi use one. All four pathways incorporate 3 C 1 {displaystyle {{ce {C1}}}} molecules into multi-carbon intermediates, then cleave one intermediate into a new C 3 {displaystyle {{ce {C3}}}} molecule. The remaining intermediates are rearranged to regenerate the original multi-carbon intermediates. Each species of methylotrophic bacteria has a single dominant assimilation pathway. The three characterized pathways for carbon assimilation are the ribulose monophosphate (RuMP) and serine pathways of formaldehyde assimilation as well as the ribulose bisphosphate (RuBP) pathway of CO2 assimilation. Unlike the other assimilatory pathways, bacteria using the RuBP pathway derive all of their organic carbon from CO 2 {displaystyle {ce {CO2}}} assimilation. This pathway was first elucidated in photosynthetic autotrophs and is better known as the Calvin Cycle. Shortly thereafter, methylotrophic bacteria who could grow on reduced C 1 {displaystyle {{ce {C1}}}} compounds were found using this pathway. First, 3 molecules of ribulose 5-phosphate are phosphorylated to ribulose 1,5-bisphosphate (RuBP). The enzyme ribulose bisphosphate carboxylase (RuBisCO) carboxylates these RuBP molecules which produces 6 molecules of 3-phosphoglycerate (PGA). The enzyme phosphoglycerate kinase phosphorylates PGA into 1,3-diphosphoglycerate (DPGA). Reduction of 6 DPGA by the enzyme glyceraldehyde phosphate dehydrogenase generates 6 molecules of the C 3 {displaystyle {{ce {C3}}}} compound glyceraldehyde-3-phosphate (GAP). One GAP molecule is diverted towards biomass while the other 5 molecules regenerate the 3 molecules of ribulose 5-phosphate.