Identification and Characterization of the Pyridomycin Biosynthetic Gene Cluster of Streptomyces pyridomyceticus NRRL B-2517

Abstract

Pyridomycin is a structurally unique antimycobacterial cyclodepsipeptide containing rare 3-(3-pyridyl)-L-alanine and 2-hydroxy-3-methylpent-2-enoic acid moieties. The biosynthetic gene cluster for pyridomycin has been cloned and identified from Streptomyces pyridomyceticus NRRL B-2517. Sequence analysis of a 42.5-kb DNA region revealed 26 putative open reading frames, including two nonribosomal peptide synthetase (NRPS) genes and a polyketide synthase gene. A special feature is the presence of a polyketide synthase-type ketoreductase domain embedded in an NRPS. Furthermore, we showed that PyrA functioned as an NRPS adenylation domain that activates 3-hydroxypicolinic acid and transfers it to a discrete peptidyl carrier protein, PyrU, which functions as a loading module that initiates pyridomycin biosynthesis in vivo and in vitro. PyrA could also activate other aromatic acids, generating three pyridomycin analogues in vivo.

Structure of the Lectin Regulatory Domain of the Cholesterol-Dependent Cytolysin Lectinolysin Reveals the Basis for Its Lewis Antigen Specificity

“…Because Le b is more widespread, it suggests that Le y is the primary ligand for initial infection and subsequent cell lysis by the bacteria. Recently, LLY was shown to belong to the CD59-binding family of CDCs, together with ILY and vaginolysin (Wickham et al, 2011). These CDCs use CD59, a GPI-anchored protein, as a receptor on the surface of cells rather than membrane cholesterol like the archetypical CDCs.…”

“…These CDCs use CD59, a GPI-anchored protein, as a receptor on the surface of cells rather than membrane cholesterol like the archetypical CDCs. It is intriguing that CD59 has fucose linkages in the outer arms of its N-linked glycan branches; hence, it is possible that the lectin domain of LLY might bind to the N-linked glycan of CD59 as well as through direct protein-protein interactions with domain 4 of the toxin (Wickham et al, 2011). In any case, the presence of the lectin domain in LLY suggests that its role is to enhance host cell recognition by guiding the toxin to fucose-rich sites on the surface of cells.…”

Totalsynthese von Nosiheptid

“…[260] Die erste Totalsynthese von Pyridomycin wurde 1989 von Kinoshita et al beschrieben. [261] Die stereoselektive Darstellung der exocyclischen (Z)-sec-Butyliden-Einheit erwies sich dabei als eine besondere…”

Identification and characterization of new family members in the tautomerase superfamily: Analysis and implications

“…TomN led to the identification of two other biosynthetic 4-OTs, Pyr5 in the pyridomycin biosynthetic pathway and SnbT in the pristinamycin biosynthetic pathway [41,42]. (Pristinamycin refers to a mixture of the chemically unrelated compounds pristinamycin I and pristinamycin II, which are co-produced by the same organism.…”