Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence

Cole, Stewart T.; Brosch, Roland; Parkhill, Julian; Garnier, Thierry; Churcher, Carol; Harris, David; Gordon, Stephen V.; Eiglmeier, Karin; Gas, Shahinaz; Barry, Clifton E.; Tekaia, Fredj; Badcock, K.; Basham, D.; Brown, D.; Chillingworth, Tracey; Connor, R.; Davies, Robert M.; Devlin, K.; Feltwell, Theresa; Gentles, S.; Hamlin, N.; Holroyd, S.; Hornsby, T.; Jagels, Kay; Krogh, Anders; McLean, Jaime; Moule, Sharon; Murphy, Lee; Oliver, Karen; Osborne, Jason W.; Quail, Michael A.; Rajandream, Marie‐Adèle; Rogers, Jane; Rutter, Simon; Seeger, Kathy; Skelton, Jason; Squares, Rob; Squares, S.; Sulston, John; Taylor, K.; Whitehead, Sally; Barrell, Bart

doi:10.1038/31159

Cited by 7,088 publications

(4,923 citation statements)

References 43 publications

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“…In contrast to the frequent observation that the components of bacterial multicomponent oxygenases are encoded in a single operon, the kshA and kshB genes encoding Ksh activity in Rhodococcus (van der Geize et al ., 2002a) or in M. tuberculosis (Cole et al ., 1998) are located far from each other in the genome. Nevertheless, using the sequence of the annotated kshA and kshB genes from Rhodococcus (van der Geize et al ., 2002a, 2008) and M. tuberculosis (Capyk et al ., 2009) as probes, we have localized the corresponding orthologues in M. smegmatis (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons

Galán

Uhía

García-Fernández

et al. 2016

Microbial Biotechnology

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SummaryA number of pharmaceutical steroid synthons are currently produced through the microbial side‐chain cleavage of natural sterols as an alternative to multi‐step chemical synthesis. Industrially, these synthons have been usually produced through fermentative processes using environmental isolated microorganisms or their conventional mutants. Mycobacterium smegmatis mc2155 is a model organism for tuberculosis studies which uses cholesterol as the sole carbon and energy source for growth, as other mycobacterial strains. Nevertheless, this property has not been exploited for the industrial production of steroidic synthons. Taking advantage of our knowledge on the cholesterol degradation pathway of M. smegmatis mc2155 we have demonstrated that the MSMEG_6039 (kshB1) and MSMEG_5941 (kstD1) genes encoding a reductase component of the 3‐ketosteroid 9α‐hydroxylase (KshAB) and a ketosteroid Δ1‐dehydrogenase (KstD), respectively, are indispensable enzymes for the central metabolism of cholesterol. Therefore, we have constructed a MSMEG_6039 (kshB1) gene deletion mutant of M. smegmatis MS6039 that transforms efficiently natural sterols (e.g. cholesterol and phytosterols) into 1,4‐androstadiene‐3,17‐dione. In addition, we have demonstrated that a double deletion mutant M. smegmatis MS6039‐5941 [ΔMSMEG_6039 (ΔkshB1) and ΔMSMEG_5941 (ΔkstD1)] transforms natural sterols into 4‐androstene‐3,17‐dione with high yields. These findings suggest that the catabolism of cholesterol in M. smegmatis mc2155 is easy to handle and equally efficient for sterol transformation than other industrial strains, paving the way for valuating this strain as a suitable industrial cell factory to develop à la carte metabolic engineering strategies for the industrial production of pharmaceutical steroids.

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Section: Resultsmentioning

confidence: 99%

Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons

Galán

Uhía

García-Fernández

et al. 2016

Microbial Biotechnology

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“…With respect to lipids, it is unique among bacteria since it has approximately 250 lipid enzymes in its genome (compared to only 50 in Escherichia coli) [17], and an unusually high number of distinct (glyco)lipids in its cell membrane and wall [18]. The natures of major components are known.…”

Section: Pathogenic Bacteria (Mycobacteria Salmonella)mentioning

confidence: 99%

Lipidomics of host–pathogen interactions

Wenk

2006

FEBS Letters

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The cell biology of intracellular pathogens (viruses, bacteria, eukaryotic parasites) has provided us with molecular information of host-pathogen interactions. As a result it is becoming increasingly evident that lipids play important roles at various stages of host-pathogen interactions. They act in first line recognition and host cell signaling during pathogen docking, invasion and intracellular trafficking. Lipid metabolism is a housekeeping function in energy homeostasis and biomembrane synthesis during pathogen replication and persistence. Lipids of enormous chemical diversity play roles as immunomodulatory factors. Thus, novel biochemical analytics in combination with cell and molecular biology are a promising recipe for dissecting the roles of lipids in host-pathogen interactions.

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“…The elucidation of the entire genome sequence of M. tuberculosis H37Rv (4.4 Mbp) in 1998 [13] allows prediction of the sequences for the expressed proteins, aiding in the conventional identification of 38 secreted proteins [14,15]. In combination with mass spectrometry (MS), now a core instrumental technology for proteomics [16,17], 49 secreted proteins have been identified out of 620 resolvable spots on 2-D gel electrophoresis by Rosenkrands et al [18].…”

mentioning

confidence: 99%

Top down characterization of secreted proteins from Mycobacterium tuberculosis by electron capture dissociation mass spectrometry

ElNaggar

Sze

et al. 2003

J. Am. Soc. Mass Spectrom.

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Secreted proteins of Mycobacterium tuberculosis are implicated in its disease pathogenesis and so are considered as potential diagnostic and vaccine candidates. The search for these has been slow, even though the entire genome sequence of M. tuberculosis is now available; of the 620 protein spots resolved by 2-D gel electrophoresis, 114 secreted proteins have been identified, but for only 13 has the primary structure been partly characterized. For comparison, in this top down mass spectrometry (MS) approach the secreted proteins were precipitated from cell culture filtrate, resuspended, and examined directly by electrospray ionization (ESI) Fourier transform MS. The ESI spectra of three precipitates showed 93, 535, and 369 molecular weight (M r ) values, for a total of 689 different values. However, only ϳ10% of these values matched (Ϯ1 Da) the DNA predicted M r values, but these identifications were unreliable. Of nine molecular ions characterized by MS/MS, only one protein match was confirmed, and its isotopic molecular ions were overlapped by those of another protein. MS/MS identified a total of ten proteins by sequence tag search, of which three were unidentified previously. The low success of M r matching was due to unusually extensive posttranslational modifications, including loss of a signal sequence, loss of the N-terminal residue, proteolytic degradation, oxidation, and glycosylation. Although in eubacteria the latter is relatively rare, a 9 kDa protein showed 7 hexose attachments and two 20 kDa proteins each had 20 attachments. For MS/MS, electron capture dissociation was especially effective. (J Am Soc Mass Spectrom 2003, 14, 253-261)

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Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence

Cited by 7,088 publications

References 43 publications

Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons

Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons

Lipidomics of host–pathogen interactions

Top down characterization of secreted proteins from Mycobacterium tuberculosis by electron capture dissociation mass spectrometry

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