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Biosynthesis of the nargenicin A1 pyrrole moiety from Nocardia sp. CS682

  • Applied genetics and molecular biotechnology
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Abstract

A number of structurally diverse natural products harboring pyrrole moieties possess a wide range of biological activities. Studies on biosynthesis of pyrrole ring have shown that pyrrole moieties are derived from l-proline. Nargenicin A1, a saturated alicyclic polyketide from Nocardia sp. CS682, is a pyrrole-2-carboxylate ester of nodusmicin. We cloned and identified a set of four genes from Nocardia sp. CS682 that show sequence similarity to the respective genes involved in the biosynthesis of the pyrrole moieties of pyoluteorin in Pseudomonas fluorescens, clorobiocin in Streptomyces roseochromogenes subsp. Oscitans, coumermycin A1 in Streptomyces rishiriensis, one of the pyrrole rings of undecylprodigiosin in Streptomyces coelicolor, and leupyrrins in Sorangium cellulosum. These genes were designated as ngnN4, ngnN5, ngnN3, and ngnN2. In this study, we presented the evidences that the pyrrole moiety of nargenicin A1 was also derived from l-proline by the coordinated action of three proteins, NgnN4 (proline adenyltransferase), NgnN5 (proline carrier protein), and NgnN3 (flavine-dependent acyl-coenzyme A dehydrogenases). Biosynthesis of pyrrole moiety in nargenicin A1 is initiated by NgnN4 that catalyzes ATP-dependent activation of l-proline into l-prolyl-AMP, and the latter is transferred to NgnN5 to create prolyl-S-peptidyl carrier protein (PCP). Later, NgnN3 catalyzes the two-step oxidation of prolyl-S-PCP into pyrrole-2-carboxylate. Thus, this study presents another example of a pyrrole moiety biosynthetic pathway that uses a set of three genes to convert l-proline into pyrrole-2-carboxylic acid moiety.

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Acknowledgments

This study was supported by Technology Development Program for Agriculture and Forestry, Ministry of Agriculture and Forestry (20100368), Republic of Korea, 2010.

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Authors and Affiliations

  1. Institute of Biomolecule Reconstruction, Sun Moon University, 100 Kalsan-ri, Tangjeonmyun, Asansi, Chungnam, 336-708, South Korea

    Sushila Maharjan, Niraj Aryal, Saurabh Bhattarai, Dinesh Koju & Jae Kyung Sohng

  2. Department of Biotechnology, Kathmandu University, P.O Box 6240, Dhulikhel, Kavre, Nepal

    Niraj Aryal & Janardan Lamichhane

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  1. Sushila Maharjan
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  2. Niraj Aryal
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  3. Saurabh Bhattarai
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  4. Dinesh Koju
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  5. Janardan Lamichhane
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  6. Jae Kyung Sohng
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Correspondence to Jae Kyung Sohng.

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Maharjan, S., Aryal, N., Bhattarai, S. et al. Biosynthesis of the nargenicin A1 pyrrole moiety from Nocardia sp. CS682. Appl Microbiol Biotechnol 93, 687–696 (2012). https://doi.org/10.1007/s00253-011-3567-x

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  • DOI: https://doi.org/10.1007/s00253-011-3567-x

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