ChemInform Abstract: Biomimetic Assembly Lines Producing Natural Product Analogues: Strategies from a Versatile Manifold to Skeletally Diverse Scaffolds

ChemInform ◽  
2016 ◽  
Vol 47 (24) ◽  
Author(s):  
Hiroki Oguri
Keyword(s):  
Natural Product ◽  
Assembly Lines

scholarly journals Evolution of combinatorial diversity in trans-acyltransferase polyketide synthase assembly lines across bacteria

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eric J. N. Helfrich ◽  
Reiko Ueoka ◽  
Marc G. Chevrette ◽  
Franziska Hemmerling ◽  
Xiaowen Lu ◽  
...  
Keyword(s):  
Natural Product ◽  
Pseudomonas Syringae ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Product Class ◽  
Assembly Lines ◽  
Evolutionary Patterns ◽  
In Trans ◽  
Global Classification ◽  
Exchange Patterns

AbstractTrans-acyltransferase polyketide synthases (trans-AT PKSs) are bacterial multimodular enzymes that biosynthesize diverse pharmaceutically and ecologically important polyketides. A notable feature of this natural product class is the existence of chemical hybrids that combine core moieties from different polyketide structures. To understand the prevalence, biosynthetic basis, and evolutionary patterns of this phenomenon, we developed transPACT, a phylogenomic algorithm to automate global classification of trans-AT PKS modules across bacteria and applied it to 1782 trans-AT PKS gene clusters. These analyses reveal widespread exchange patterns suggesting recombination of extended PKS module series as an important mechanism for metabolic diversification in this natural product class. For three plant-associated bacteria, i.e., the root colonizer Gynuella sunshinyii and the pathogens Xanthomonas cannabis and Pseudomonas syringae, we demonstrate the utility of this computational approach for uncovering cryptic relationships between polyketides, accelerating polyketide mining from fragmented genome sequences, and discovering polyketide variants with conserved moieties of interest. As natural combinatorial hybrids are rare among the more commonly studied cis-AT PKSs, this study paves the way towards evolutionarily informed, rational PKS engineering to produce chimeric trans-AT PKS-derived polyketides.

scholarly journals Thiocysteine lyases as polyketide synthase domains installing hydropersulfide into natural products and a hydropersulfide methyltransferase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Song Meng ◽  
Andrew D. Steele ◽  
Wei Yan ◽  
Guohui Pan ◽  
Edward Kalkreuter ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Assembly Line ◽  
Polyketide Synthase ◽  
Genome Mining ◽  
Assembly Lines ◽  
Biologically Relevant ◽  
Peptide Synthetase ◽  
Adenosyl Methionine

AbstractNature forms S-S bonds by oxidizing two sulfhydryl groups, and no enzyme installing an intact hydropersulfide (-SSH) group into a natural product has been identified to date. The leinamycin (LNM) family of natural products features intact S-S bonds, and previously we reported an SH domain (LnmJ-SH) within the LNM hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line as a cysteine lyase that plays a role in sulfur incorporation. Here we report the characterization of an S-adenosyl methionine (SAM)-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin (GNM) biosynthesis, discovery of hydropersulfides as the nascent products of the GNM and LNM hybrid NRPS-PKS assembly lines, and revelation of three SH domains (GnmT-SH, LnmJ-SH, and WsmR-SH) within the GNM, LNM, and weishanmycin (WSM) hybrid NRPS-PKS assembly lines as thiocysteine lyases. Based on these findings, we propose a biosynthetic model for the LNM family of natural products, featuring thiocysteine lyases as PKS domains that directly install a -SSH group into the GNM, LNM, or WSM polyketide scaffold. Genome mining reveals that SH domains are widespread in Nature, extending beyond the LNM family of natural products. The SH domains could also be leveraged as biocatalysts to install an -SSH group into other biologically relevant scaffolds.

Novel Characters of Myxobacterial Modular Natural Product Assembly Lines*

2012 ◽  
Vol 39 (6) ◽  
pp. 525-539 ◽  
Author(s):  
Li-Ping ZHU ◽  
Zhi-Feng Li ◽  
Kui HAN ◽  
Shu-Guang LI ◽  
Yue-Zhong LI
Keyword(s):  
Natural Product ◽  
Assembly Lines ◽  
Product Assembly
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