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Chen M, Pang B, Du YN, et al. Characterization of the metallo-dependent amidohydrolases responsible for "auxiliary" leucinyl removal in the biosynthesis of 2,2'-bipyridine antibiotics. Synth Syst Biotechnol. 2017;2(2):137-146doi: 10.1016/j.synbio.2017.07.002.
Chen, M., Pang, B., Du, Y. N., Zhang, Y. P., & Liu, W. (2017). Characterization of the metallo-dependent amidohydrolases responsible for "auxiliary" leucinyl removal in the biosynthesis of 2,2'-bipyridine antibiotics. Synthetic and systems biotechnology, 2(2), 137-146. https://doi.org/10.1016/j.synbio.2017.07.002
Chen, Ming, et al. "Characterization of the metallo-dependent amidohydrolases responsible for "auxiliary" leucinyl removal in the biosynthesis of 2,2'-bipyridine antibiotics." Synthetic and systems biotechnology vol. 2,2 (2017): 137-146. doi: https://doi.org/10.1016/j.synbio.2017.07.002
Chen M, Pang B, Du YN, Zhang YP, Liu W. Characterization of the metallo-dependent amidohydrolases responsible for "auxiliary" leucinyl removal in the biosynthesis of 2,2'-bipyridine antibiotics. Synth Syst Biotechnol. 2017 Jul 13;2(2):137-146. doi: 10.1016/j.synbio.2017.07.002. eCollection 2017 Jun. PMID: 29062971; PMCID: PMC5636949.
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Synth Syst Biotechnol. 2017 Jul 13;2(2):137-146. doi: 10.1016/j.synbio.2017.07.002. eCollection 2017 Jun.

Characterization of the metallo-dependent amidohydrolases responsible for "auxiliary" leucinyl removal in the biosynthesis of 2,2'-bipyridine antibiotics.

Synthetic and systems biotechnology

Ming Chen, Bo Pang, Ya-Nan Du, Yi-Peng Zhang, Wen Liu

Affiliations

  1. State Key Laboratory of Bioorganic and Nature Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
  2. State Key Laboratory of Microbial Metabolism, School of Life Science & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
  3. Huzhou Center of Bio-Synthetic Innovation, 1366 Hongfeng Road, Huzhou 313000, China.

PMID: 29062971 PMCID: PMC5636949 DOI: 10.1016/j.synbio.2017.07.002

Abstract

2,2'-Bipyridine (2,2'-BiPy) is an attractive core structure present in a number of biologically active natural products, including the structurally related antibiotics caerulomycins (CAEs) and collismycins (COLs). Their biosynthetic pathways share a similar key 2,2'-BiPy-l-leucine intermediate, which is desulfurated or sulfurated at C5, arises from a polyketide synthase/nonribosomal peptide synthetase hybrid assembly line. Focusing on the common off-line modification steps, we here report that the removal of the "auxiliary" l-leucine residue relies on the metallo-dependent amidohydrolase activity of CaeD or ColD. This activity leads to the production of similar 2,2'-BiPy carboxylate products that then receive an oxime functionality that is characteristic for both CAEs and COLs. Unlike many metallo-dependent amidohydrolase superfamily proteins that have been previously reported, these proteins (particularly CaeD) exhibited a strong zinc ion-binding capacity that was proven by site-specific mutagenesis studies to be essential to proteolytic activity. The kinetics of the conversions that respectively involve CaeD and ColD were analyzed, showing the differences in the efficiency and substrate specificity of these two proteins. These findings would generate interest in the metallo-dependent amidohydrolase superfamily proteins that are involved in the biosynthesis of bioactive natural products.

Keywords: 2,2′-Bipyridine antibiotics; Amidohydrolase; Caerulomycins; Collismycins

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