Mining of the Pyrrolamide Antibiotics Analogs in Streptomyces netropsis Reveals the Amidohydrolase-Dependent “Iterative Strategy” Underlying the Pyrrole Polymerization

Abstract

In biosynthesis of natural products, potential intermediates or analogs of a particular compound in the crude extracts are commonly overlooked in routine assays due to their low concentration, limited structural information, or because of their insignificant bio-activities. This may lead into an incomplete and even an incorrect biosynthetic pathway for the target molecule. Here we applied multiple compound mining approaches, including genome scanning and precursor ion scan-directed mass spectrometry, to identify potential pyrrolamide compounds in the fermentation culture of Streptomyces netropsis. Several novel congocidine and distamycin analogs were thus detected and characterized. A more reasonable route for the biosynthesis of pyrrolamides was proposed based on the structures of these newly discovered compounds, as well as the functional characterization of several key biosynthetic genes of pyrrolamides. Collectively, our results implied an unusual “iterative strategy” underlying the pyrrole polymerization in the biosynthesis of pyrrolamide antibiotics.

Combination therapy with polymyxin B and netropsin against clinical isolates of multidrug-resistant Acinetobacter baumannii

“…MS spectrum analysis of the Compound 1 from AN130070 extracted from S. netropsis SN01 showed two major peaks at m/z 431.2264 and 431.2291, and was consistent with the known spectrum for netropsin ( Fig. 2b ) 17 18 .…”

“…The 1 H NMR inspection confirmed chemical structure of the Compound 1 compared with 1 H NMR data of netropsin ( Fig. S4 ) 18 . MS spectrum analysis of the Compound 1 from AN130070 extracted from S. netropsis SN01 showed two major peaks at m/z 431.2264 and 431.2291, and was consistent with the known spectrum for netropsin ( Fig.…”

Ornithine Transcarbamylase ArgK Plays a Dual role for the Self-defense of Phaseolotoxin Producing Pseudomonas syringae pv. phaseolicola

“…High resolution MS analysis was carried out in a positive mode on a Thermo Scientific LTQ XL Orbitrap mass spectrometer as described previously 38 . PHTs samples from the culture supernatants of P. syringae pv.…”

Gene Flow and Molecular Innovation in Bacteria

“…MBT166[34]. Finally, and perhaps the most unusual example of this phenomenon is the reciprocally-dependent BGCs in Streptomyces netropsis DSM40846 that encode for a suite of at least three pyrrolamides[35, 36]. This all-for-one strategy, described as a natural example of combinatorial biosynthesis[36], is a stark contrast to the one-for-all or diversity-generating biosynthetic pathways that have been dissected for decades, and it provides another confirmation of the summation model for assembling BGCs.…”