| Full text | |
| Author(s): |
Sigrist, Renata
;
Luhavaya, Hanna
;
McKinnie, Shaun M. K.
;
da Silva, Amanda Ferreira
;
Jurberg, Igor D.
;
Moore, Bradley S.
;
de Oliveira, Luciana Gonzaga
Total Authors: 7
|
| Document type: | Journal article |
| Source: | ACS Chemical Biology; v. 15, n. 4, p. 11-pg., 2020-04-17. |
| Abstract | |
Alpiniamide A is a linear polyketide produced by Stieptomyces endophytic bacteria. Despite its relatively simple chemical structure suggestive of a linear assembly line biosynthetic construction involving a hybrid polyketide synthase-nonribosomal peptide synthetase enzymatic protein machine, we report an unexpected nonlinear synthesis of this bacterial natural product. Using a combination of genomics, heterologous expression, mutagenesis, isotope-labeling, and chain terminator experiments, we propose that alpiniamide A is assembled in two halves and then ligated into the mature molecule. We show that each polyketide half is constructed using orthogonal biosynthetic strategies, employing either cis- or trans-acyl transferase mechanisms, thus prompting an alternative proposal for the operation of this PKS-NRPS. (AU) | |
| FAPESP's process: | 16/25735-1 - Mining Streptomyces sp. B1 metabolites: isolation and characterization |
| Grantee: | Renata Sigrist |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate (Direct) |
| FAPESP's process: | 19/10564-5 - Assessing the beneficial aspects of endophytic actinobacteria: expanding the Brazilian microorganisms genome codified natural products |
| Grantee: | Luciana Gonzaga de Oliveira |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/12727-5 - Genome mining in Streptomyces |
| Grantee: | Luciana Gonzaga de Oliveira |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/01013-4 - Mining a t1PKS-transAT PKS-NRPS in Streptomyces sp. genome |
| Grantee: | Renata Sigrist |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock |
| Grantee: | Arlene Gonçalves Corrêa |
| Support Opportunities: | Research Grants - Applied Research Centers Program |
| FAPESP's process: | 17/24017-0 - Application of Isoxazolones in Organic Synthesis |
| Grantee: | Igor Dias Jurberg |
| Support Opportunities: | Regular Research Grants |