Caerulomycins (CAEs) and collismycins (COLs), which mainly differ in sulfur decoration, are two groups of structurally similar natural products containing a 2,2'-bipyridine (2,2'-BP) core, derivatives of which have been widely used in chemistry. The biosynthetic pathways of CAEs and COLs remain elusive. In this work, cloning of the CAE biosynthetic gene cluster allowed us to mine a highly conserved gene cluster encoding COL biosynthesis in a Streptomyces strain that was previously unknown as a 2,2'-BP producer. In vitro and in vivo investigations into the biosynthesis revealed that CAEs and COLs share a common paradigm featuring an atypical hybrid polyketide synthase/nonribosomal peptide synthetase system that programs the 2,2'-BP formation. This likely involves an unusual intramolecular cyclization/rearrangement sequence, and a difference in processing of the sulfhydryl group derived from the same precursor cysteine drives the biosynthetic route toward CAEs or COLs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/ja3016457 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovery of caerulomycin/collismycin-type 2,2'-bipyridine natural products in the genomic era.
J Ind Microbiol Biotechnol
March 2019
State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence on Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Lingling Road, 200032, Shanghai, China.
2,2'-Bipyridine (2,2'-BP) is the unique molecular scaffold of the bioactive natural products represented by caerulomycins (CAEs) and collismycins (COLs). CAEs and COLs are highly similar in the chemical structures in which their 2,2'-BP cores typically contain a di- or tri-substituted ring A and an unmodified ring B. Here, we summarize the CAE and COL-type 2,2'-BP natural products known or hypothesized to date: (1) isolated using methods traditional for natural product characterization, (2) created by engineering the biosynthetic pathways of CAEs or COLs, and (3) predicted upon bioinformatics-guided genome mining.
View Article and Find Full Text PDFCharacterization of the metallo-dependent amidohydrolases responsible for "auxiliary" leucinyl removal in the biosynthesis of 2,2'-bipyridine antibiotics.
Synth Syst Biotechnol
June 2017
State Key Laboratory of Bioorganic and Nature Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Article Synopsis
- 2,2'-Bipyridine (2,2'-BiPy) is a core structure found in antibiotics like caerulomycins (CAEs) and collismycins (COLs), which share a common biosynthetic pathway involving a key intermediate.
- The focus of the study is on the metallo-dependent amidohydrolase enzymes, CaeD and ColD, which remove an auxiliary l-leucine residue, resulting in similar carboxylate products that are further modified.
- The research highlights the strong zinc-binding capacity of these enzymes, particularly CaeD, which is crucial for their proteolytic activity, and analyzes differences in their efficiency and substrate specificity.
Caerulomycins and collismycins share a common paradigm for 2,2'-bipyridine biosynthesis via an unusual hybrid polyketide-peptide assembly Logic.
J Am Chem Soc
June 2012
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China.
Caerulomycins (CAEs) and collismycins (COLs), which mainly differ in sulfur decoration, are two groups of structurally similar natural products containing a 2,2'-bipyridine (2,2'-BP) core, derivatives of which have been widely used in chemistry. The biosynthetic pathways of CAEs and COLs remain elusive. In this work, cloning of the CAE biosynthetic gene cluster allowed us to mine a highly conserved gene cluster encoding COL biosynthesis in a Streptomyces strain that was previously unknown as a 2,2'-BP producer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!