niiicholas
Posts: 319
Joined: May 2002
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This is a big enough topic to deserve a thread separate from the origin of information or the origin of particular systems.
Short version: there is lots of evidence that multiple-parts-required metabolic pathways have originated via known evolutionary processes, in human and even lab lifetimes.
Here is a synthesis article I just came across:
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Curr Opin Struct Biol 2002 Jun;12(3):374-82
Pathway evolution, structurally speaking.
Rison SC, Thornton JM.
Department of Biochemistry and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Small-molecule metabolism forms the core of the metabolic processes of all living organisms. As early as 1945, possible mechanisms for the evolution of such a complex metabolic system were considered. The problem is to explain the appearance and development of a highly regulated complex network of interacting proteins and substrates from a limited structural and functional repertoire. By permitting the co-analysis of phylogeny and metabolism, the combined exploitation of pathway and structural databases, as well as the use of multiple-sequence alignment search algorithms, sheds light on this problem. Much of the current research suggests a chemistry-driven 'patchwork' model of pathway evolution, but other mechanisms may play a role. In the future, as metabolic structure and sequence space are further explored, it should become easier to trace the finer details of pathway development and understand how complexity has evolved.
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Then of course we have:
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Trends in Biochemical Sciences
Volume 25, Issue 6, 1 June 2000, Pages 261-265
Evolution of a metabolic pathway for degradation of a toxic xenobiotic: the patchwork approach
Shelley D. Copley
The pathway for degradation of the xenobiotic pesticide pentachlorophenol in Sphingomonas chlorophenolica probably evolved in the past few decades by the recruitment of enzymes from two other catabolic pathways. The first and third enzymes in the pathway, pentachlorophenol hydroxylase and 2,6-dichlorohydroquinone dioxygenase, may have originated from enzymes in a pathway for degradation of a naturally occurring chlorinated phenol. The second enzyme, a reductive dehalogenase, may have evolved from a maleylacetoacetate isomerase normally involved in degradation of tyrosine. This apparently recently assembled pathway does not function very well: pentachlorophenol hydroxylase is quite slow, and tetrachlorohydroquinone dehalogenase is subject to severe substrate inhibition.
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An important update:
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J Bacteriol 2003 Jan;185(1):302-10
A Previously Unrecognized Step in Pentachlorophenol Degradation in Sphingobium chlorophenolicum Is Catalyzed by Tetrachlorobenzoquinone Reductase (PcpD).
Dai M, Rogers JB, Warner JR, Copley SD.
The first step in the pentachlorophenol (PCP) degradation pathway in Sphingobium chlorophenolicum has been believed for more than a decade to be conversion of PCP to tetrachlorohydroquinone. We show here that PCP is actually converted to tetrachlorobenzoquinone, which is subsequently reduced to tetrachlorohydroquinone by PcpD, a protein that had previously been suggested to be a PCP hydroxylase reductase. pcpD is immediately downstream of pcpB, the gene encoding PCP hydroxylase (PCP monooxygenase). Expression of PcpD is induced in the presence of PCP. A mutant strain lacking functional PcpD has an impaired ability to remove PCP from the medium. In contrast, the mutant strain removes tetrachlorophenol from the medium at the same rate as does the wild-type strain. These data suggest that PcpD catalyzes a step necessary for degradation of PCP, but not for degradation of tetrachlorophenol. Based upon the known mechanisms of flavin monooxygenases such as PCP hydroxylase, hydroxylation of PCP should produce tetrachlorobenzoquinone, while hydroxylation of tetrachlorophenol should produce tetrachlorohydroquinone. Thus, we proposed and verified experimentally that PcpD is a tetrachlorobenzoquinone reductase that catalyzes the NADPH-dependent reduction of tetrachlorobenzoquinone to tetrachlorohydroquinone.
Introduction
Pentachlorophenol (PCP) is a widely used and highly toxic wood preservative. It was first introduced as a pesticide in 1936 (7) and is not known to be a natural product. Despite its recent introduction into the environment and its high toxicity, several strains of Sphingobium chlorophenolicum (previously Sphingomonas chlorophenolica) (24) that can mineralize PCP have been identified. The best studied of these are strains ATCC 39723 (19), RA-2 (23), and UG30 (6). It appears that S. chlorophenolicum has assembled a new metabolic pathway capable of converting this anthropogenic compound into a recognizable metabolite. Our previous studies suggest that this pathway has been assembled by patching together enzymes from at least two different metabolic pathways (8). PCP hydroxylase (PCP monooxygenase; EC 1.14.13.50) and 2,6-dichlorohydroquinone dioxygenase may have originated from enzymes that hydroxylated a naturally occurring chlorinated phenol and then cleaved the resulting hydroquinone. Tetrachlorohydroquinone (TCHQ) dehalogenase appears to have originated from a glutathione-dependent double bond isomerase such as maleylacetoacetate isomerase or maleylpyruvate isomerase (which are involved in degradation of tyrosine and benzoate, respectively) (2). If this pathway has evolved recently in response to the introduction of PCP into the environment, then it would not be expected to perform at the high level characteristic of pathways that have evolved over periods of millions or billions of years. Indeed, the PCP degradation pathway shows signs of immaturity in several respects. First, PCP hydroxylase, the first enzyme in the pathway, is very inefficient in vitro (P. M. Kiefer and S. D. Copley, unpublished data), and appears to severely limit the flux of PCP through the pathway in vivo (17). Second, TCHQ dehalogenase is profoundly inhibited by its aromatic substrate (K. Anandarajah, P. M. Kiefer, and S. D. Copley, unpublished data). Third, TCHQ dehalogenase expression is not regulated in tandem with the other known enzymes in the pathway but is apparently constitutive (21). All of these findings are consistent with the idea that the PCP degradation pathway has been patched together rather recently and has not been fine-tuned to perform as effectively as do most bacterial metabolic pathways.
The gene encoding PCP hydroxylase (pcpB) is immediately upstream of two additional genes. pcpR encodes a regulatory protein that responds to PCP (5). pcpD, which is immediately downstream of pcpB, resembles genes for the reductase components of two-component oxygenases, some of which hydroxylate aromatic compounds. Based upon this resemblance, it has been proposed that PcpD is a reductase that facilitates the hydroxylation of PCP by PCP hydroxylase (19), and the annotation of PcpD in GenBank states that it is PCP 4-monooxygenase reductase. We suspected that this assignment was incorrect because PCP hydroxylase is a flavin monooxygenase, and such enzymes do not generally require reductases. Consequently, we undertook studies to determine whether PcpD is required for degradation of PCP. We find that transcription of pcpD is induced by PCP, as previously reported for pcpA (29) and pcpB (20). A mutant strain in which PcpD has been knocked out is able to remove PCP from the medium when it is present at low concentrations, but not when it is present at high concentrations. In contrast, the knockout strain can remove tetrachlorophenol (TCP) from the medium as well as the wild-type strain, even at high concentrations. These results suggest that PcpD may catalyze a step that is critical for degradation of PCP but not TCP and therefore must involve the chlorine at the 4 position of PCP. Based upon the expected mechanism of the hydroxylase reaction, the sequence of PcpD, and our experimental results, we propose that PcpD is a tetrachlorobenzoquinone (TCBQ) reductase required for degradation of PCP but not TCP.
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