Biosynthesis of Trehangelin in Polymorphospora rubra K07–0510: Identification of Metabolic Pathway to Angelyl‐CoA

Abstract

Trehangelins are trehalose angelates discovered from endophytic actinomycete Polymorphospora rubra K07-0510. We identified the trehangelin biosynthetic gene cluster, including genes that encode a glycoside hydrolase-like protein (thgC), α-amylase (thgD), 3-ketoacyl-ACP synthase III (thgI), 3-ketoacyl-ACP reductase (thgK), enoyl-CoA hydratase (thgH) and acyl transferase (thgJ). Heterologous expression of thgH, thgI, thgJ and thgK confirmed the importance of these genes in the biosynthesis of trehangelin A. Enzymatic activity studies showed that ThgI catalyses the condensation of acetyl-CoA and methylmalonyl-CoA to 2-methylacetoacetyl-CoA (MAA-CoA), ThgK catalyses NADPH-dependent reduction of MAA-CoA to 3-hydroxy-2-methylbutyryl-CoA (HMB-CoA) and ThgH catalyses the dehydration of HMB-CoA to angelyl-CoA (AN-CoA). This is the first report on the elucidation of the enzymatic formation of AN-CoA.

Improvement Effects of Trehangelin A on High-Fat Diet Causing Metabolic Clinical Conditions

“…THG-A was originally isolated from the cultured broth of P. rubra K07-0510, and the structure was determined. 6,7) One of the biological activities of THG-A is its anti-oxidative activity against hemolysis of RBCs induced by light-activated pheophorbide α activation. 6) Notably, the anti-oxidative activity of THG-A is stronger than that of the same dose of ascorbic acid.…”

“…The structures of these trehangelins comprise a trehalose moiety and two angelic acid moieties. 6) In addition, the THG-A biosynthetic gene cluster of P. rubra K07-0510 was identified. 7) Trehangelins have anti-oxidative effect that act to prevent hemolysis of red blood cells (RBCs) induced by light-activated pheophorbide α activation in in vitro models.…”

“…6) In addition, the THG-A biosynthetic gene cluster of P. rubra K07-0510 was identified. 7) Trehangelins have anti-oxidative effect that act to prevent hemolysis of red blood cells (RBCs) induced by light-activated pheophorbide α activation in in vitro models. 6) Furthermore, trehangelins have shown no in vitro cytotoxic activities at concentrations below 100 µg/mL.…”

“…7) Trehangelins have anti-oxidative effect that act to prevent hemolysis of red blood cells (RBCs) induced by light-activated pheophorbide α activation in in vitro models. 6) Furthermore, trehangelins have shown no in vitro cytotoxic activities at concentrations below 100 µg/mL. Of note, P. rubra K07-0510 produces markedly more THG-A than THG-B and THG-C, and the anti-oxidative effect of THG-A was shown to be the strongest among the trehangelins, as well as stronger than that of the same dose of ascorbic acid.…”

Identification and Interrogation of the Herbicidin Biosynthetic Gene Cluster: First Insight into the Biosynthesis of a Rare Undecose Nucleoside Antibiotic

“…15 However, the only known angelyl ester substituent in bacterial metabolites is found in SF2575 and heliosupine, where it is hypothesized to be of polyketide origin. 16 Likewise, there has been little work 17 done to determine whether 2a and 2b originate from the catabolism of l -isoleucine or arise though polyketide-medicated biosynthetic pathways.…”