Biosynthetic pathway of 24-membered macrolactam glycoside incednine

Takaishi, Makoto; Kudo, Fumitaka; Eguchi, Tadashi

doi:10.1016/j.tet.2008.05.024

Cited by 14 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ML694-90F3 as an inhibitor of antiapoptotic function in Bcl-2/Bcl-xL oncoproteins (Figure ) . Our previous study on incednine biosynthesis revealed that its 24-membered macrolactam aglycon moiety was biosynthesized through the polyketide pathway using a unique amino acid starter unit, possibly a 3-aminobutyrate equivalent that was derived from l -glutamic acid . In the present study, to elucidate the missing link between l -glutamate and the unique amino acid starter unit, several additional deuterium amino acid feeding experiments were conducted.…”

mentioning

confidence: 74%

A Unique Pathway for the 3-Aminobutyrate Starter Unit from l-Glutamate through β-Glutamate during Biosynthesis of the 24-Membered Macrolactam Antibiotic, Incednine

2012

Self Cite

View full text Add to dashboard Cite

Incednine is a 24-membered macrolactam antibiotic produced by Streptomyces sp. ML694-90F3. A previous study demonstrated that its unique nitrogen-containing starter unit was derived from L-glutamate. To elucidate the missing link between L-glutamate and the starter unit, deuterium labeled amino acid feeding experiments were conducted. These experiments revealed that 3-[3-(2)H]aminobutyrate and β-[2,2,4,4-(2)H(4)]glutamate were incorporated into the starter moiety. The results indicate that a novel decarboxylation of β-glutamate to give 3-aminobutyrate is involved in incednine biosynthesis.

show abstract

mentioning

confidence: 74%

A Unique Pathway for the 3-Aminobutyrate Starter Unit from l-Glutamate through β-Glutamate during Biosynthesis of the 24-Membered Macrolactam Antibiotic, Incednine

2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, there are limited reports of xylosamines in glycosides. For example, some diamino xylosides have been found in certain antibiotics (36,37), one of which was isolated from members of Nocardiopsis species (36). Whether the pathogenic Bacillus species also synthesize antimicrobial xylosamine-glycosides, however, is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of a New UDP-sugar, UDP-2-acetamido-2-deoxyxylose, in the Human Pathogen Bacillus cereus Subspecies cytotoxis NVH 391-98

Glushka

Lee

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have identified an operon and characterized the functions of two genes from the severe food-poisoning bacterium, Bacillus cereus subsp. cytotoxis NVH 391-98, that are involved in the synthesis of a unique UDP-sugar, UDP-2-acetamido-2-deoxyxylose (UDP-N-acetyl-xylosamine, UDP-XylNAc). UGlcNAcDH encodes a UDP-N-acetyl-glucosamine 6-dehydrogenase, converting UDP-N-acetylglucosamine (UDP-GlcNAc) to UDP-N-acetyl-glucosaminuronic acid (UDP-GlcNAcA). The second gene in the operon, UXNAcS, encodes a distinct decarboxylase not previously described in the literature, which catalyzes the formation of UDPXylNAc from UDP-GlcNAcA in the presence of exogenous NAD ؉ . UXNAcS is specific and cannot utilize UDP-glucuronic acid and UDP-galacturonic acid as substrates. UXNAcS is active as a dimer with catalytic efficiency of 7 mM ؊1 s ؊1. The activity of UXNAcS is completely abolished by NADH but unaffected by UDP-xylose. A real-time NMR-based assay showed unambiguously the dual enzymatic conversions of UDP-GlcNAc to UDP-GlcNAcA and subsequently to UDP-XylNAc. From the analyses of all publicly available sequenced genomes, it appears that UXNAcS is restricted to pathogenic Bacillus species, including Bacillus anthracis and Bacillus thuringiensis. The identification of UXNAcS provides insight into the formation of UDP-XylNAc. Understanding the metabolic pathways involved in the utilization of this amino-sugar may allow the development of drugs to combat and eradicate the disease.A food poisoning outbreak in France in 1998 led to the isolation of a new strain of Bacillus cereus subsp. cytotoxis NVH 391-98 (1). This rod-shaped Gram-positive bacterium causes a disease that initially produces emetic (nausea and vomiting)-like symptoms, and/or in more severe cases produces a diarrheal form that causes abdominal cramps and diarrhea (2). Similar to its close relatives, the notorious human pathogen Bacillus anthracis and the insecticidal Bacillus thuringiensis, the B. cereus strain can form spores. Due to its cell surface, a spore can survive harsh conditions (e.g. soil and air), and when the environment becomes appropriate, it will germinate, resulting in a vegetative cell that can produce emetic toxin and different enterotoxins (3). The cell surfaces of many pathogenic bacteria are composed of diverse and complex carbohydrate structures, some of which are known virulence factors. Indeed, different B. cereus peptidoglycans and glycoproteins were isolated, and some were reported to play a role in spore formation and infection (3-5). It is also clear, however, that among those different types of Bacillus glycans, many are not yet fully characterized. Regardless, compared with the limited knowledge of these glycan structures, the pathways leading to their biosyntheses are still elusive. To identify such metabolic pathways, we initially decided to look for putative genes encoding enzymes involved in the synthesis of glycan precursors (i.e. nucleotide-sugars).Different UDP-GlcA 2 decarboxylases with distinct functions exist in both eukaryotes...

show abstract

“…The core structure of the macrotermycins ( 5 ) belongs to a family of macrolactam polyketides that include incednine, 10 vicenistatin, 11 silvalactam, 12 heronamides, 13 verticilactam, 14 ciromicins, 15 mirilactams and lobosamides. 16 Both 1 and 3 can be viewed as polyene precursors for intramolecular cycloadditions leading to 2 and 4 , respectively, and the relevant reaction pathways, whether enzymatically catalyzed or occurring spontaneously either in situ or during purification, are being investigated.…”

mentioning

confidence: 99%

Macrotermycins A–D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39

et al. 2017

View full text Add to dashboard Cite

Bioassay-guided metabolomic analyses led to the characterization of four new 20-membered glycosylated polyketide macrolactams – macrotermycins A-D – from a termite-associated actinomycete, Amycolatopsis sp. M39. M39’s sequenced genome revealed the macrotermycin’s putative biosynthetic gene cluster. Macrotermycins A and C had antibacterial activity against human-pathogenic S. aureus and of greater ecological relevance, they also had selective antifungal activity against a fungal parasite of the termite fungal garden.

show abstract

Biosynthetic pathway of 24-membered macrolactam glycoside incednine

Cited by 14 publications

References 22 publications

A Unique Pathway for the 3-Aminobutyrate Starter Unit from l-Glutamate through β-Glutamate during Biosynthesis of the 24-Membered Macrolactam Antibiotic, Incednine

A Unique Pathway for the 3-Aminobutyrate Starter Unit from l-Glutamate through β-Glutamate during Biosynthesis of the 24-Membered Macrolactam Antibiotic, Incednine

Biosynthesis of a New UDP-sugar, UDP-2-acetamido-2-deoxyxylose, in the Human Pathogen Bacillus cereus Subspecies cytotoxis NVH 391-98

Macrotermycins A–D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39

Contact Info

Product

Resources

About