Combinatorial biosynthesis yields novel hybrid argimycin P alkaloids with diverse scaffolds in Streptomyces argillaceus

Autor: Suhui Ye, Giovanni Ballin, Ignacio Pérez‐Victoria, Alfredo F. Braña, Jesús Martín, Fernando Reyes, José A. Salas, Carmen Méndez
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Microbial Biotechnology, Vol 15, Iss 12, Pp 2905-2916 (2022)
Druh dokumentu: article
ISSN: 1751-7915
DOI: 10.1111/1751-7915.14167
Popis: Abstract Coelimycin P1 and argimycins P are two types of polyketide alkaloids produced by Streptomyces coelicolor and Streptomyces argillaceus, respectively. Their biosynthesis pathways share some early steps that render very similar aminated polyketide chains, diverging the pathways afterwards. By expressing the putative isomerase cpkE and/or the putative epoxidase/dehydrogenase cpkD from the coelimycin P1 gene cluster into S. argillaceus wild type and in argimycin mutant strains, five novel hybrid argimycins were generated. Chemical characterization of those compounds revealed that four of them show unprecedented scaffolds (quinolizidine and pyranopyridine) never found before in the argimycin family of compounds. One of these compounds (argimycin DM104) shows improved antibiotic activity. Noticeable, biosynthesis of these quinolizidine argimycins results from a hybrid pathway created by combining enzymes from two different pathways, which utilizes an aminated polyketide chain as precursor instead of lysine as it occurs for other quinolizidines.
Databáze: Directory of Open Access Journals
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