Caboxamycin biosynthesis pathway and identification of novel benzoxazoles produced by cross‐talk in Streptomyces sp. NTK 937. Issue 4 (18th April 2017)

• Record Type: Journal Article
• Authors: Losada, Armando A.; Cano‐Prieto, Carolina; García‐Salcedo, Raúl; Braña, Alfredo F.; Méndez, Carmen; Salas, José A.; Olano, Carlos
• Other Names: Morgenroth Eberhard guestEditor.; Flemming Hans‐Curt guestEditor.; Azeredo Joana guestEditor.; Melo Luis F. guestEditor.; Espinosa Manuel guestEditor.; Whiteley Marvin guestEditor.; Briandet Romain guestEditor.
• Is Part Of: Microbial biotechnology. Volume 10:Issue 4(2017:Jul.)
• Page Start: 873
• Page End: 885
• Publication Date: 2017-04-18
• Subjects: Microbial biotechnology -- Periodicals; Biotechnology; Microbiology; 660.62
• DOI: 10.1111/1751-7915.12716
• Languages: English
• ISSNs: 1751-7915

Abstract

Summary: Streptomyces sp. NTK937, producer of benzoxazole antibiotic caboxamycin, produces in addition a methyl ester derivative, O ‐methylcaboxamycin. Caboxamycin cluster, comprising one regulatory and nine structural genes, has been delimited, and each gene has been individually inactivated to demonstrate its role in the biosynthetic process. The O ‐methyltransferase potentially responsible for O ‐methylcaboxamycin synthesis would reside outside this cluster. Five of the genes, cbxR, cbxA, cbxB, cbxD and cbxE, encoding a SARP transcriptional regulator, salicylate synthase, 3‐oxoacyl‐ACP‐synthase, ACP and amidohydrolase, respectively, have been found to be essential for caboxamycin biosynthesis. The remaining five structural genes were found to have paralogues distributed throughout the genome, capable of partaking in the process when their cluster homologue is inactivated. Two of such paralogues, cbxC' and cbxI', coding an AMP‐dependent synthetase‐ligase and an anthranilate synthase, respectively, have been identified. However, the other three genes might simultaneously have more than one paralogue, given that cbxF (DAHP synthase), cbxG (2, 3‐dihydro‐2, 3‐dihydroxybenzoate dehydrogenase) and cbxH (isochorismatase) have three, three and five putative paralogue genes, respectively, of similar function within the genome. As a result of genetic manipulation, a novel benzoxazole (3′‐hydroxycaboxamycin) has been identified in the salicylate synthase‐deficient mutant strain ΔcbxA. 3′‐hydroxycaboxamycin derives from the cross‐talk between the caboxamycin and enterobactin pathways. Abstract : Streptomyces sp. NTK936 presents a versatile metabolism for the biosynthesis of bezoxazole compounds of the caboxamycin type. This includes the presence of several paralogs of the caboxamycin biosynthesis structural genes and others that can interact by cross‐talk with the caboxamycin pathway. This metabolic network allows the production of at least two caboxamycin derivatives: O‐methyl‐caboxamycin and 3'‐hydroxy‐caboxamycin.