Nonlinear Biosynthetic Assembly of Alpiniamide by ... - BV FAPESP
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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Nonlinear Biosynthetic Assembly of Alpiniamide by a Hybrid cis/trans-AT PKS-NRPS

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Author(s):
Sigrist, Renata [1] ; Luhavaya, Hanna [2] ; McKinnie, Shaun M. K. [2] ; da Silva, Amanda Ferreira [1] ; Jurberg, Igor D. [1] ; Moore, Bradley S. [3, 2] ; de Oliveira, Luciana Gonzaga [1]
Total Authors: 7
Affiliation:
[1] Univ Campinas Unicamp, Inst Chem, Dept Organ Chem, BR-13083970 Campinas, SP - Brazil
[2] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA 92093 - USA
[3] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 - USA
Total Affiliations: 3
Document type: Journal article
Source: ACS Chemical Biology; v. 15, n. 4, p. 1067-1077, APR 17 2020.
Web of Science Citations: 0
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: 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: 17/24017-0 - Application of Isoxazolones in Organic Synthesis
Grantee:Igor Dias Jurberg
Support Opportunities: Regular Research Grants
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 - Research Centers in Engineering Program
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: 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)