Methanobactin: Metal binding properties, physiological function and biosynthesis

dc.contributor.advisor Alan A. DiSpirito Baral, Bipin
dc.contributor.department Biochemistry, Biophysics and Molecular Biology 2018-08-11T15:38:26.000 2020-06-30T03:02:35Z 2020-06-30T03:02:35Z Sun Jan 01 00:00:00 UTC 2017 2001-01-01 2017-01-01
dc.description.abstract <p>Methanobactins (mbs) are low molecular mass (< 1300 Da) modified peptides</p> <p>secreted by many methanotrophs or methane oxidizing bacteria to sequester copper from the</p> <p>environment. To date, methanobactin has been structurally characterized from six</p> <p>methanotrophs and can be divided into two groups. Group I methanobactins are represented</p> <p>by methanobactins from Methylosinus trichosporium OB3b and Methylosinus sp. LW4. This</p> <p>group is characterized by the presence of two oxazolone rings with adjacent thioamide</p> <p>groups. Two nitrogens from the oxazolone rings and two sulfurs from the thioamide groups</p> <p>come together to form a copper coordination site in distorted tertrahedral geometry. This</p> <p>group of methanobactin also has two cysteines in the mature protein that form a stable</p> <p>disulfide bond. The second group is composed of methanobactins from four different</p> <p>Methylocystis species. This group of methanobactins has a hairpin like structure following</p> <p>copper binding with sulfate group attached to serine or threonine and is structurally more</p> <p>dynamic than group I methanobactins. This group is also characterized by the presence of a</p> <p>C-terminal oxazolone ring with an associated thioamide and either an N-terminal</p> <p>imidazolone or pyrazinedione group and an associated thioamide.</p> <p>The first part of this dissertation is focused on the study of methanobactin binding to various non-copper metals such as mercury and gold and the role of that binding of noncopper</p> <p>metals has on the physiology of methanotrophs. The second part of this dissertation is</p> <p>focused on understanding the post-translational modifications required for methanobactin.</p> <p>Until recently, the biosynthesis was assumed to be via a non-ribosomal peptide synthase or</p> <p>polyketide synthase. However, during the course of my dissertation, we determined that</p> <p>methanobactin is indeed produced ribosomally and post-translationally modified. I show in</p> <p>this dissertation that TonB-dependent transporter gene in the methanobactin gene cluster is</p> <p>involved in the uptake of copper-bound methanobactin. In addition, we demonstrate that</p> <p>mbnN is involved in the deamination of the N-terminal oxazolone ring, a post-translational</p> <p>modification required in the formation of the N-terminal oxazolone ring in the methanobactin from Methylosinus trichosporium OB3b.</p> <p>The results and methods used in this research would further help determine the role of</p> <p>other genes involved in biosynthesis of methanobactin and bioengineer methanobactin for</p> <p>various human and animal health purposes. In light of recent evidence of methanobactin</p> <p>being effective chelator of excess copper in Wilson’s disease in rat models, understanding the</p> <p>biosynthesis of methanobactin has become more important.</p>
dc.format.mimetype application/pdf
dc.identifier archive/
dc.identifier.articleid 6263
dc.identifier.contextkey 11050916
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath etd/15256
dc.language.iso en
dc.source.bitstream archive/|||Fri Jan 14 20:38:14 UTC 2022
dc.subject.disciplines Biochemistry
dc.subject.keywords Biosynthesis of methanobactin
dc.subject.keywords Copper
dc.subject.keywords Mercury
dc.subject.keywords Methane monooxygenase
dc.subject.keywords Methanobactin
dc.subject.keywords Methanotrophs
dc.title Methanobactin: Metal binding properties, physiological function and biosynthesis
dc.type article
dc.type.genre dissertation
dspace.entity.type Publication
relation.isOrgUnitOfPublication faf0a6cb-16ca-421c-8f48-9fbbd7bc3747 Biochemistry dissertation Doctor of Philosophy
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