Biology subjects

Sumang, F. A.

Publications and source records attributed to Sumang, F. A..

3 recordsLinked to original sources

bioRxiv2026

Hierarchical Cytochrome P450 Oxidations Program Persiathiacin Assembly

Thiopeptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that form complex bioactive scaffolds through extensive enzymatic tailoring. The polyglycosylated thiopeptides persiathiacins, exhibit potent activity against multidrug-resistant Mycobacterium tuberculosis (Mtb) and methicillin-resistant Staphylococcus aureus (MRSA). The persiathiacin biosynthetic gene cluster encodes six cytochrome P450 (CYP) enzymes, but the logic of their oxidative modifications was unknown. Here, we establish a protoplast-based genetic system for Actinokineospora and systematically assign functions to all P450s. We demonstrate that PerX hydroxylates the central thiazole, PerV installs the third indole-core crosslink required for macrocyclization, and PerT, not PerU, catalyses indole N-hydroxylation. Combined gene inactivation and metabolite profiling reveal a hierarchical enzymatic sequence leading to the mature scaffold prior to sugar installation. Notably, the intermediate accumulating in the{Omega} perX mutant exhibits enhanced anti-M. tuberculosis potency compared to persiathiacin A (IC50 = 0.07 vs 1.5 {micro}g mL-1). These results define the enzymatic logic and temporal organization of persiathiacin biosynthesis, providing a conceptual framework for rational diversification of complex thiopeptide natural products.

microbiology↗

bioRxiv2025

An O-acetylated derivative of piericidin A1 produced by Kitasatospora sp. A2-31 has potent activity against the cacao mirid bug, Helopeltis bakeri Poppius

There is an increasing demand for novel biopesticides to protect agricultural products and improve yields. To address this need, extracts from a library of Actinomycetes collected in the Philippines were evaluated against the cacao mirid bug, Helopeltis bakeri Poppius. Analysis of an active ethyl acetate extract from Kitasatospora sp. A2-31 led to the identification of a novel metabolite acetylpiericidin A1 (3) along with the known natural products piericidin A1 (1), piericidin A5 (2), chromomycin A2 (4), chromomycin A3 (5), and olivomycin A (6). Acetylpiericidin A1 demonstrated 100 % mortality against H. bakeri, while other metabolites exhibited either weak or no activity. Whole genome sequencing followed by bioinformatics analysis identified a gene downstream of the piericidin biosynthetic gene cluster that encodes a putative acetyltransferase proposed to catalyze acetylation of the C10 hydroxyl group of piericidin A1. The involvement of this gene in acetylpiericidin A1 biosynthesis was confirmed by (i) introducing an additional copy under the control of the ermE* promoter into Kitasatospora sp. A2-31, resulting in elevated production levels and (ii) through an in vitro enzymatic assay of the corresponding purified recombinant enzyme.

microbiology↗

bioRxiv2019

Pentamycin biosynthesis in Philippine Streptomyces sp. S816: Cytochrome P450-catalysed installation of the C-14 hydroxyl group

Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomo-niasis and mixed infections. Chemical instability has hindered its wide-spread application and development as a drug. Here we report the identification of Streptomyces sp. S816, isolated from Philippine mangrove soil, as a pentamycin producer. Genome sequence analysis identified the putative pentamycin biosynthetic gene cluster, which shows a high degree of similarity to the gene cluster responsible for filipin III biosynthesis. The ptnJ gene, which is absent from the filipin III biosynthetic gene cluster, was shown to encode a cytochrome P450 capable of converting filipin III to pentamycin. This confirms that the cluster directs pentamycin biosynthesis, paving the way for biosynthetic engineering approaches to the production of pentamycin analogues. Several other Streptomyces genomes were found to contain ptnJ orthologues clustered with genes encoding polyketide synthases that appear to have similar architectures to those responsible for the assembly of filipin III and pentamycin, suggesting pentamycin production may be common in Streptomyces species.

biochemistry↗